However, after infection or treatment with H  polygyrus AgS, F9 o

However, after infection or treatment with H. polygyrus AgS, F9 or F17, the percentage of apoptotic cells decreased. The percentage of apoptotic CD8+ cells remained

unchanged. Taken together, during infection and after cell activation by TCR and CD28 receptors, H. polygyrus antigens reduced both the proliferation and apoptosis of CD4+cells. Seventeen fractions were separated from the somatic homogenate of the H. polygyrus complete antigen with molecular range from 11 to 130 kDa and differences in activity between fractions were observed in cell culture. In naïve mice, the percentage of apoptotic cells decreased after stimulation of MLN cells with AgS (from 51% to 34.9%) and with antigenic fractions (Figure 4a). Infection buy Torin 1 with H. polygyrus also significantly reduced the percentage of apoptotic cells. Spontaneous apoptosis in RPMI medium decreased from 51% in uninfected mice to 22,8% after infection and only 6.3% of CD4+ cells were in apoptosis after stimulation with F9. The percentage of apoptotic cells was reduced in all examined populations

of T cells; CD4+CD25−, CD4+CD25hi, CD3+CD8+ in MLN (Figure 4b). Cells isolated on day 12 post infection responded distinctly to complete antigen (AgS) and to each antigen fraction. Treatment of cells with fraction F9, F13 and F17 deeply reduced apoptosis. In contrast, when fractions F6 and F19 were added, the percentage of apoptotic cells increased (data not shown). The lowest level of apoptosis was observed in CD3+CD4+ population. Only 5% of cells underwent apoptosis after treatment with fraction F9. Apoptosis of CD4+CD25hi and CD3+CD8+ cells was higher, 30% and 18% respectively, but was still lower in infected than in control mice (Figure 4b). Fraction F9 contrary to F17, was the most potent to reduce the percentage of apoptotic cells of infected mice. Overall, H. polygyrus somatic antigen and its fractions inhibited apoptosis Tyrosine-protein kinase BLK both in naïve and infected mice. To examine apoptosis signalling pathways, apoptosis of MLN cells was induced by dexamethasone (DEX), a synthetic corticosteroid and by rTNF-α,

and the percentage of apoptotic cells was evaluated both in uninfected and infected mice. All examined cell populations were sensitive to DEX which induced apoptosis (Figure 5). In naïve mice, 60% of CD4+ cells were apoptotic and only AgS inhibited cell death; fractions F9 and F17 even increased the percentage of apoptotic cells. Response of CD4+CD25hi cells was also significant and after treatment with DEX more than 80% of cells underwent apoptosis. After infection with H. polygyrus apoptosis of these cells was reduced by 40% and even by 60% after restimulation with the nematode antigens. CD3+CD8+ cells were less sensitive to DEX and approximately 60% of cells were apoptotic. Apoptosis of these cells was inhibited both in control and infected mice after exposition to H. polygyrus antigens.

We will also present novel insights into the function of Th cells

We will also present novel insights into the function of Th cells in tissues. We will especially focus on Th-cell subsets in the skin as a model organ to investigate the full spectra of functional Th-cell diversity. The first approach to define distinct Th-cell subsets relates to the pioneering work of Mosmann and Coffman, who observed that Th cells could be distinguished according their secreted signature cytokines (reviewed in [1]). They defined two distinct subsets, Th1 cells and Th2 cells, Selleck Lumacaftor that differed in that Th1 cells produced IFN-γ and Th2 cells produced IL-4

(Fig. 1). This dichotomous paradigm of Th1 and Th2 subsets persisted for more than 20 years, until about 7 years ago when the emergence of Th17 cells challenged

this simplistic dualism of only two Th-cell subsets [2]. The definition of Th17 cells also sparked the concept of a broader heterogeneity in the Th-cell immune compartment (reviewed in [2, 3]). Following the discovery of Th17 cells, which secrete their name-giving cytokine IL-17, other Th-cell subsets emerged on the scene, including Th22 [4-6] and Th9 cells [7], which express the signature cytokines IL-22 and IL-9, respectively. This system of categorization is well-appreciated and immunology textbooks use these terms to distinguish between Th-cell subsets. However, reality is a bit more complex and immunologists are puzzled by the fact that some Th cells are not restricted to these firm lineage boundaries and co-express signature cytokines of distinct subsets in parallel. Th1 or Th2 cells co-secreting IL-17 are two examples of Decitabine nmr Th-cell subsets that do not fit into the original concept of Th-cell classification. This observation has been attributed to the plasticity of Th-cell subsets.

It is still debated how the phenotype of these “plastic” cells is regulated, and if they indeed have to be regarded as distinct subsets [8-10]. This is especially important with respect to the fact that these “hybrid” T cells change their function upon acquisition of additional cytokine secretion properties. That is, IL-17- PAK6 and IFN-γ-co-expressing cells are considered to be pathogenic in settings of autoimmunity [11], while IL-17+IFN-γ− cells have even been assigned anti-inflammatory functions [12]. In the future, the original Th classification concept will be further challenged by new detection techniques that allow deciphering the full secretome of cells. This overwhelming information will ultimately lead to the question if categorization according to secreted factors is still reasonable. Another widely used possibility to classify Th cells is the assignment of lineage-specific transcription factors, which are responsible for the initiation of subset-specific differentiation programs and maintenance of the phenotype (Fig. 1). Tbet, GATA3, and RORC are well-established transcriptional regulators of Th1, Th2, and Th17 cells, respectively.

However, the use of an echinocandin + liposomal amphotericin B fo

However, the use of an echinocandin + liposomal amphotericin B formulation is a better option as indicated by both animal and human data.[31-35] All authors declare no conflicts of interest. “
“Immunocompromised patients have CT99021 manufacturer a high risk for invasive fungal diseases (IFDs). These infections are mostly life-threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Empirical treatment is regarded as the standard of care for granulocytopenic

patients who remain febrile despite broad-spectrum antibiotics. However, this strategy can bear a risk of overtreatment and subsequently induce toxicities and unnecessary treatment costs. Pre-emptive antifungal therapy is now increasingly used to close the time gap between delayed initiation for proven disease and empirical treatment for anticipated infection without further laboratory or radiological evidence of fungal disease. Currently, some new non-invasive microbiological and laboratory methods, like the Aspergillus-galactomannan sandwich-enzyme immunoassay (Aspergillus GM-ELISA), 1,3-β-d-glucan assay or PCR techniques

have been developed for a better diagnosis selleckchem and determination of target patients. The current diagnostic approaches to fungal infections and the role of the revised definitions for invasive fungal infections, now IFDs, will be discussed in this review as well as old and emerging approaches to empirical, pre-emptive and targeted antifungal therapies in patients with haemato-oncological malignancies. “
“Prosthetic joint infections (PJI) are rarely due to fungal agents and if so they are mainly caused by Candida strains. This case represents a PJI caused by a multi-drug resistant Pseudallescheria apiosperma, with poor in vivo response to itraconazole and voriconazole. This case differs also by the way of infection, since the Digestive enzyme joint infection did

not follow a penetrating trauma. In the majority of cases, Scedosporium extremity infections remain local in immunocompetent individuals. We report a persistent joint infection with multiple therapeutic failures, and subsequent amputation of the left leg. Detailed clinical data, patient history, treatment regime and outcome of a very long-lasting (>4 years) P. apiosperma prosthetic knee infection in an immunocompetent, 61-year-old male patient are presented with this case. The patient was finally cured by the combination of multiple and extensive surgical interventions and prolonged antifungal combination therapy with voriconazole and terbinafine. Prosthetic joint infection (PJI) is mainly caused by bacteria and rarely by human-pathogenic yeast such as Candida strains.1–4Aspergillus fumigatus5 or other filamentous fungi are only exceptionally involved.

In vitro experiments conducted

with human cell lineages s

In vitro experiments conducted

with human cell lineages showed an increase in cell survival when IRE1α activity is sustained for longer periods. This suggests that the IRE1/XBP-1 axis of the UPR pathway might balance the decision between life and death towards the anti-apoptotic side [37]. In contrast with IRE1, prolonged activation of PERK diminishes cell survival and this effect is associated with increased levels of CHOP mRNA and apoptosis markers, such as poly ADP-ribose polymerase [38]. Altogether, these results suggest that IRE1α and PERK have opposite roles on cell survival during ER stress. Several physiological events alter ER homeostasis, activating the UPR pathway: calcium unbalance, diminished glucose levels, tissue ischaemia, viral infections, and mutations that disturb protein folding. The ER lumen is an oxidative environment that is rich in calcium 5-Fluoracil order and provides the ideal conditions for formation

of disulphide bond and proper protein folding. Depletion of calcium storages interferes with the functioning of chaperones BiP and calnexin [39, 40], inhibits glycosylation by enzyme UDP-glucose:glycoprotein buy Venetoclax glucosyltransferase (UGGT), and diminishes the interaction of calreticulin and calnexin with misfolded proteins [41]. All these lead to improper folding of proteins, resulting in ER stress and activation of UPR. Diminished glucose levels activate the UPR pathway because folding and assembly of proteins require large amounts of energy. Besides, glycosylation of some proteins is a crucial step for their proper folding. An oligosaccharide chain (GlcNA2Man9Glc3) is added to nascent proteins. Misfolded proteins are held within the ER lumen by calnexin/calreticulin for re-glycosylation by the enzyme UGGT [42]. During ischaemia, the diminished blood flow results in local hypoglycemia leading to

accumulation of misfolded proteins within the ER Leukotriene-A4 hydrolase through a similar mechanism [43, 44]. Viruses contribute to acute ER protein overload, leading to ER stress and consequent activation of the UPR pathway. Viruses also cause an increase in the metabolic rate from usage of the cellular machinery, resulting in higher usage of ATP and temporary depletion of glucose, altogether activating the UPR pathway [45–48]. Certain mutations that prevent the protein chain to fold in the most stable conformation also result in ER stress. Misfolded/unfolded proteins tend to associate and form aggregates that are toxic for the cell and/or result in premature degradation of these proteins via proteasome. Several neurodegenerative diseases have been associated to accumulation of misfolded proteins, such as Parkinson, Alzheimer, and Huntington [49–51]. Terminal differentiation of B lymphocytes into plasma cells also activates the UPR pathway and this activation is associated with the latter cells demand for increased levels of immunoglobulin synthesis and expansion of the ER to accommodate the immunoglobulin overload.

“Hookworms are one of the most

prevalent parasites

“Hookworms are one of the most

prevalent parasites of humans in developing countries, but we know relatively little about the immune response generated to hookworm infection. This can be attributed to a lack of permissive animal models and a relatively small research community compared with those of the more high-profile parasitic diseases. However, recently, research has emerged on the development of vaccines to control hookworm infection and the use of hookworm to treat autoimmune and allergic disorders, contributing to a greater understanding of the strategies used by hookworms to modulate the host’s immune response. A substantial body of research on the immunobiology of hookworms originates from Australia, so this review will summarize the current status of the field with a particular emphasis on research carried out ‘down under’. Ku-0059436 in vivo Hookworms are one of the most common

parasites of humans, with around 740 million people infected worldwide. Although they cause little mortality, heavy infections can cause iron-deficiency anaemia, growth retardation and low birth weight (1). Hookworms are most prevalent in South America, sub-Saharan Africa and East Asia; however, up until the second half of the 20th century, they were also common in the southern states of USA, Europe (2) and Australia, where they still affect some remote aboriginal communities (3). The two major anthropophilic hookworm species are Necator americanus Luminespib in vivo and Ancylostoma duodenale. The more common parasite, on which the majority of studies have consequently been carried out, is N. americanus. Hookworms are soil-transmitted helminths: infective larvae burrow through the skin and are activated in the process, after which they migrate through the heart and lungs to the gut, where they mature to adults, feed on host blood and produce eggs which are deposited in the faeces. Deposited eggs then develop to infective larvae, completing the life cycle (1). The host Isotretinoin must therefore mount an immune response against a number of different parasite

stages during a hookworm infection, and the parasite in turn has a number of opportunities to manipulate the host immune system. We will not dwell on the life cycle of the parasite in this review – for more detail, see (4). The immunology of human hookworm infection has not received as much focus as that of other helminth parasites of humans, such as schistosomes and filariae. The reasons for this include the relatively low mortality caused by hookworms, the difficulty/expense in maintaining the life cycle in a suitable animal model and the inability of any of the major species of hookworms to reach maturity in mice. This has especially been a problem in Australia where the best laboratory model, the hamster, is not permitted to be maintained in the country because of quarantine regulations. Consequently, Australian hookworm research has focussed on human immunology, and especially experimental or zoonotic human infections.

“The epidemiological and pathogenic relationship between B

“The epidemiological and pathogenic relationship between Bordetella pertussis and Bordetella parapertussis, the two causes of whooping cough (pertussis), is unclear. We hypothesized that B. pertussis, due to its immunosuppressive activities, might enhance B. parapertussis infection when the two species were present in a coinfection of the respiratory tract. The dynamics of this

relationship were examined using the mouse intranasal inoculation model. Infection check details of the mouse respiratory tract by B. parapertussis was not only enhanced by the presence of B. pertussis, but B. parapertussis significantly outcompeted B. pertussis in this model. Staggered inoculation of the two organisms revealed that the advantage for B. parapertussis is established at an early stage of infection. Coadministration of PT enhanced B. parapertussis single infection, but had no

effect on mixed infections. Mixed infection with a PT-deficient B. pertussis strain did not enhance B. parapertussis infection. Interestingly, the depletion of airway macrophages reversed the competitive relationship between these two organisms, but the depletion of neutrophils had no effect on mixed infection or B. parapertussis infection. We conclude that B. pertussis, through the action Roxadustat in vivo of PT, can enhance a B. parapertussis infection, possibly by an inhibitory effect on innate immunity. The acute respiratory disease whooping cough (or pertussis) is caused by the gram-negative coccobacillus Bordetella pertussis, which binds to ciliated cells of the respiratory tract. However, a shorter and milder form of the disease is also caused by Bordetella Methisazone parapertussis (Heininger et al., 1994). Data suggest that B. parapertussis is the causative agent of a significant proportion of whooping cough cases in some global locations, including several European countries

(Watanabe & Nagai, 2004). In a clinical setting, it is hard to distinguish between these two pathogens, and involves costly laboratory tests such as PCR assays (Tatti et al., 2008). The treatment of infection is the same regardless of which of these two species of Bordetella is the infective agent, and therefore, tests to identify the causative pathogen are not always conducted. Mixed outbreaks and coinfection of patients with these two organisms have also been seen in clinical studies (Mertsola, 1985; Iwata et al., 1991), and there is little understanding of the epidemiological and pathogenic relationship between the two. Both of these pathogens are restricted to human hosts, although a distinct group of B. parapertussis strains that evolved independently (B. parapertussisov) infects sheep, causing a chronic nonprogressive pneumonia (Porter et al., 1994; Diavatopoulos et al., 2005). Bordetella pertussis and B.

Gems are the sites of the maturation of spliceosomes, which are <

Gems are the sites of the maturation of spliceosomes, which are learn more composed of uridylate-rich (U) snRNAs (small nuclear RNAs) and protein complex, small nuclear ribonuclearprotein (snRNP). Spliceosomes regulate the splicing of pre-mRNA and are classified into the major or minor classes, according to the consensus sequence

of acceptor and donor sites of pre-mRNA splicing. Although the major class of spliceosomes regulates most pre-mRNA splicing, minor spliceosomes also play an important role in regulating the splicing or global speed of pre-mRNA processing. A mouse model of spinal muscular atrophy, in which the number of Gems is decreased, shows fewer subsets U snRNAs. Interestingly, in the central nervous system, U snRNAs belonging to the minor spliceosomes are markedly reduced. In ALS, the U12 snRNA is decreased only in the tissue affected by ALS and not in other tissues. Although the molecular mechanisms underlying the decreased U12 snRNA resulting in cell dysfunction and cell death in motor neuron diseases remain unclear, these findings

suggest that the disturbance of nuclear bodies and minor splicing may underlie the common molecular pathogenesis of motor neuron diseases. Motor neuron system selectivity is a major mystery of motor neuron diseases. Although research has shown that the pathology is not restricted to motor neurons but also extends into other PI3K Inhibitor Library research buy neurons as well as glial cells, the selective vulnerability of motor neurons is a characteristic feature of amyotrophic lateral sclerosis (ALS). However, the molecular mechanism underlying the vulnerability of the motor neuron system has not been fully explained. To clarify this issue, researchers must clarify what distinguishes the motor neuron. Researchers have identified several molecular markers and physiological characters that distinguish motor neurons from others.[1] However, the morphology and location of the cell have been used as the most significant signature for identifying motor neurons in tissues. The

cells of the CNS are diverse and complex, and they are mostly defined by their shape, size PTK6 and location in the tissues. The complexity of the cells reflects the complexity of the cells’ RNAs. The diversity of RNAs results in part from the methylation of DNA, but studies have shown that other mechanisms also control cell-specific RNA diversity. A higher structure of the nucleus, chromatin, and nuclear bodies, is another mechanism that regulates the cell-specific RNA diversity. Recent findings have revealed that chromatin has a unique structure and location in the nucleus in each type of cell. The chromatin structure is strongly associated with the diversity of RNA.[2] Moreover, the other intranuclear structures also play an important role in maintaining cell function and cell survival. Thus, the intracellular location or character of nuclear bodies may also differ in each cell type.

The choice of antigen format impacts upon the frequency of respon

The choice of antigen format impacts upon the frequency of responding T cells. An islet extract comprises the full spectrum of islet antigens, whereas at the other extreme synthetic peptides comprise one, sometimes two, epitopes [30,31]. Hence, one would expect responses to islet lysates to be detected more readily because a larger pool of potentially responsive T cells is present in the blood. However, tissue extracts are susceptible to protease digestion Romidepsin cost and other modifications that may alter the immunogenicity of the tissue. Furthermore, the composition of tissue extracts cannot be defined in the same ways as peptides or recombinant

proteins. Recombinant protein preparations can vary in quality and purity, and these changes can impact upon T cell responses [32]. Synthetic peptides have also Selleckchem BTK inhibitor been reported to give misleading results. Attempts to detect CD8+ T cell responses to proinsulin-derived peptides lead to CD4+ T cell responses against a minor (<5%) peptide contaminant [33]. Responses to other peptide contaminants

have been described in attempts to detect T cell responses to other autoimmune diseases [34]. Given the low frequency of antigen-specific T cells, assays designed to measure islet autoantigen-specific T cell function are particularly susceptible to the technical problems outlined above. The solution is to use the appropriate controls to demonstrate the islet antigen specificity

of the T cell responses being measured, and thorough testing with samples from individuals with and without T1D, ifenprodil to demonstrate disease specificity. Broadly, current assays for measuring islet antigen-specific T cell responses measure cytokine production, T cell proliferation or the frequency of epitope-specific T cells using HLA-peptide multimers with or without in vitro expansion. Examples of each type of assay, their strengths and weaknesses, are discussed below. While we have highlighted published assays with which the authors have direct experience, it should be noted that there are many variations on each assay format. Furthermore, description of an assay here does not imply that it is, in some way, endorsed by the Immunology of Diabetes Society (IDS). At this point ‘head-to-head’ comparisons of the different assays are beginning to be published, but it is not clear [35] which assay, if any, is the ‘best’ assay. Indeed, the most appropriate assay may differ depending upon the aim of the analysis. For example, the best assays for detecting islet antigen-specific T cell responses in the blood of people at risk of T1D may not be the most appropriate assay for monitoring changes in epitope-specific T cell function following antigen-based therapy. Clearly, much work is required before there is sufficient evidence to promote one assay above any other. Background.

For cytofluorimetric analysis (FACSCalibur, Becton Dickinson

For cytofluorimetric analysis (FACSCalibur, Becton Dickinson

& Co, Mountain View, CA, USA), cells were stained with the appropriate unlabeled mAbs followed selleck kinase inhibitor by PE-conjugated isotype-specific goat anti-mouse secondary Ab (Invitrogen-Life Technologies, Carlsbad, CA, USA; Southern Biotechnology Associated, Birmingham, AL). For the evaluation of apoptotic/dead cells, the AV/PI staining kit (Bender Systems, Wien, Austria) was used following the manufacturer instructions. The gating strategies to assess AV/PI staining or to evaluate NK-receptor expression are shown in Supporting Information Fig. 3. For CD107 mobilization, 2 × 105 NK cells cultured in IL-2 either under hypoxic or normoxic conditions were cocultured with 2 × 105 target cells (FO-1 or P815 cells) in 96 V-bottom well

plates. PE-conjugated Selleck Selumetinib anti-CD107a mAb was added in each well at the onset of the coculture. NK cells and target cells were coincubated for 4 h at 37°C in 5% CO2; after the first hour of coincubation, Golgi Stop (Becton Dickinson) was added. Cells were then washed in PBS with 2 mM EDTA and stained with the appropriate fluorochrome-conjugated mAbs. Analysis of CD107a surface expression in NK cells mixed with FO-1 cell line was done on cells double-stained with FITC-conjugated anti-CD45 and allophycocyanin-conjugated anti-CD56 mAbs. To detect spontaneous degranulation, a control sample without target cells was included. NK-cell incubation with the FcγR+ P815 murine cell line was done either in the absence or in the presence of IgG1 mAbs P-type ATPase specific for the receptors indicated in the text. Analysis of CD107a surface expression in NK cells mixed with P815 cell line was

done on cells stained with APC-conjugated anti-CD56 mAb. NK-cell populations were tested for cytolytic activity in a 4-h 51Cr-release assay against either two human melanoma cell lines (i.e. FO-1 and MeCoP), the B-EBV cell line 721.221 (i.e. 221), or the FcγR+ P815 murine cell line. The concentration of the various mAbs added in the redirected killing and in the ADCC experiments was 1 μg/mL. The E:T ratios are indicated in the figures. Statistical analyses were performed using the Prism software package (release 5.00; GraphPad Software). Statistical significance was evaluated by two-tailed paired Student’s t-test. A p value of less than 0.05 (*), less than 0.01 (**), or less than 0.001 (***) was considered statistically significant. This work was supported by grants awarded by Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.): IG project numbers 5282 (M.V.), 10565 (L.V.), 10225 (L.M.), MFAG project number 6384 (G.P.), and “Special Program Molecular Clinical Oncology 5×1000” project number 9962 (L.M.); Ministero dell’Istruzione, Università e Ricerca (MIUR): MIUR-FIRB 2003 project RBLA039LSF-001 (L.M.

Finally, plates were read using a microplate ELISA reader (Spectr

Finally, plates were read using a microplate ELISA reader (Spectramax M5, Molecular Devices, Sunnyvale, CA, USA) at 450 nm and soft Max Pro 5 software (Molecular Devices) with a cutoff of 0.1 absorbance value. Spleen and lung cells

(1 × 106 cells/well) were seeded into 24-well tissue culture plates in 500 μL of RPMI-1640 medium supplemented with 10% FBS, 25mM Na-HEPES, 2 mM l-glutamine, 1 mM sodium pyruvate, 100 U/mL penicillin, and 100 U/mL streptomycin, and subsequently treated with 5 μg/mL M. tuberculosis WCL at 37°C with 5% CO2. After 72 h, cell-free culture supernatant was collected and analyzed for INF-γ and IL-2, by ELISA (eBioScience) according to the manufacturer’s instruction. Six weeks after the M. tuberculosis Torin 1 datasheet infection, small sections of the

GPCR Compound Library cost right and left lung, removed prior to harvesting the tissue for CFU determination, were fixed in 10% neutral buffered formalin (Fisher Scientific, Fair Lawn, NJ, USA) at room temperature overnight, and then embedded in paraffin (Leica, Richmond, IL, USA). The sections were taken at 4 μm thickness and stained with H&E for microscopic analysis. To determine histopathological changes, all sections were scored for severity by scanning entire fields in three sections of each tissue per mouse based on the extent of granulomatous inflammation as described [32]: 0 = no lesion, 1 = minimal lesion (1–10% area of tissue in section involved), 2 = mild lesion (11–30% area involved), 3 = moderate lesion (31–50% area involved), 4 = marked lesion (50–80% area involved), 5 = severe lesion (>80% area involved). The data obtained was analyzed by ANOVA and Student paired t-test. Differences between means were assessed for significance by Tukey’s test. A value of p ≤ 0.05 was considered significant. Fossariinae The

computer program GraphPad PRISM 5 was used for the analysis. This work was supported through the grant RO1AI052439 from the National Institute of Allergy and Infectious Diseases. We thank the University of Notre Dame’s Histology Core for the processing and staining of the tissue samples. The authors declare no financial or commercial conflict of interest. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. “
“Department of Infectious Diseases, Oslo University Hospital – Ulleval, Oslo, Norway Top Institute Food and Nutrition, Wageningen, The Netherlands Innate and adaptive mucosal defense mechanisms ensure a homeostatic relationship with the large and complex mutualistic gut microbiota.