The mucosal immune system: from control of inflammation to protection against infections

Kaiserlian, Dominique; Cerf‐Bensussan, Nadine; Hosmalin, Anne

doi:10.1189/jlb.0105053

Cited by 23 publications

(16 citation statements)

References 48 publications

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“…In health, the GI tract maintains a balance between immune tolerance and rapid responsiveness [45], [46], which is perturbed in HIV infection [4].…”

Section: Discussionmentioning

confidence: 99%

Exogenous HIV-1 Nef Upsets the IFN-γ-Induced Impairment of Human Intestinal Epithelial Integrity

et al. 2011

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BackgroundThe mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIV-induced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins have been detected in several cell types of the intestinal mucosa. In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on human epithelial cell line.Methodology/Principal FindingsWe used unstimulated or IFN-γ-stimulated Caco-2 cells, as a model for homeostatic and inflamed gastrointestinal tracts, respectively. We investigated the effect of exogenous recombinant Nef on monolayer integrity analyzing its uptake, transepithelial electrical resistance, permeability to FITC-dextran and the expression of tight junction proteins. Moreover, we measured the induction of proinflammatory mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal epithelial permeability and upset the IFN-γ-induced reduction of transepitelial resistance, interfering with tight junction protein expression. Moreover, Nef inhibited IFN-γ-induced apoptosis and up-regulated TNF-α, IL-6 and MIP-3α production by Caco-2 cells while down-regulated IL-10 production. The simultaneous exposure of Caco-2 cells to Nef and IFN-γ did not affect cytokine secretion respect to untreated cells. Finally, we found that Nef counteracted the IFN-γ induced arachidonic acid cascade.Conclusion/SignificanceOur findings suggest that exogenous Nef, perturbing the IFN-γ-induced impairment of intestinal epithelial cells, could prolong cell survival, thus allowing for accumulation of viral particles. Our results may improve the understanding of AIDS pathogenesis, supporting the discovery of new therapeutic interventions.

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“…In health, the GI tract maintains a balance between immune tolerance and rapid responsiveness [45], [46], which is perturbed in HIV infection [4].…”

Section: Discussionmentioning

confidence: 99%

Exogenous HIV-1 Nef Upsets the IFN-γ-Induced Impairment of Human Intestinal Epithelial Integrity

et al. 2011

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“…Although several studies have focused on the adaptive immune system of mucosal surfaces of the female reproductive tract, scant attention has been focused on the innate immune factors in vaginal secretions (41)(42)(43)(44). Evidence is accumulating that vaginal epithelia are more than simple physical barriers to protect against invading pathogens (15,45,46).…”

Section: Discussionmentioning

confidence: 99%

Cationic Polypeptides Are Required for Anti-HIV-1 Activity of Human Vaginal Fluid

Venkataraman

Cole

Svoboda

et al. 2005

The Journal of Immunology

142

167

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Mucosal surfaces of the vagina are the portals for heterosexual transmission of HIV-1 and therefore play a fundamental role in the pathogenesis of primary infection. In the search for direct biological evidence for the role of human vaginal fluid in innate host defense, we characterized the anti-HIV-1 function of cationic polypeptides within minimally manipulated vaginal fluid. In the current study we revealed that vaginal fluid confers intrinsic anti-HIV-1 properties against both X4 and R5 strains of HIV-1 and could protect against HIV-1 infection and reduce proviral genome integration in organotypic cultures of human cervicovaginal tissue. The majority of this activity was contained in the cationic polypeptide fraction, and the depletion of cationic polypeptides using a selective cation exchange resin ablated most of the intrinsic activity against HIV-1. By adding the cationic polypeptide fraction to depleted vaginal fluid, we were able to restore activity against HIV-1. Using a proteomic approach, we identified 18 cationic polypeptides within vaginal fluid, nearly all of which are either known antimicrobials or have other purported roles in host defense. Interestingly, physiologic concentrations of 13 of the cationic polypeptides were not active alone against HIV-1, yet in concert they partially restored the anti-HIV-1 activity of cation-depleted vaginal fluid. These results suggest that synergism between cationic polypeptides is complex, and full anti-HIV-1 activity probably involves the aggregate of the cationic peptides and proteins in vaginal fluid.

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“…Other studies have pointed out that the C3H/HeJ mouse strain is more susceptible to the induction of food allergy than other non-deficient mouse strains which makes it a valuable strain for food allergy research (Frossard et al, 2004a;Frossard et al, 2004b;Kaiserlian et al, 2005;Sicherer and Sampson, 2006). However studies of Bashir et al (2004) and Berin et al (2006) on several mouse strains of different genetic backgrounds including the TLR4 + -and TLR4 --C3H, C57Bl/6 or BALB/c mice sensitised either with BLG or peanut extract demonstrated that T-cell responses, propensity to develop an allergic reaction and intensity of the IgE response were under H2-linked genetic control and depend on both the TLR4 status of the mice and the nature of the antigen.…”

Section: Transgenic Animal (Mouse) Modelsmentioning

confidence: 99%

Scientific Opinion on the assessment of allergenicity of GM plants and microorganisms and derived food and feed

2010

EFSA Journal

392

231

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The weight-of-evidence, case-by-case approach is considered the most appropriate way of assessing the allergenicity of genetically modified (GM) food and feed. This scientific opinion discusses various aspects to increase the strength and accuracy of this approach, including the latest developments pertaining to clinical aspects of allergic reactions, structural aspects of GM food and feed and in silico approaches, as well as IgE binding studies and cell-based methods, profiling techniques and animal models. In this context, conclusions and recommendations are provided to update and complement current risk assessment strategies for the allergenicity assessment of newly expressed protein(s) and whole GM food and feed. In summary, it is recommended that with regard to the search for sequence homology and structural similarities, the local alignment method with a known allergen with a threshold of 35% sequence identity over a window of at least 80 amino acids is considered a minimal requirement. When IgE binding tests are considered necessary, e.g. when there is sequence homology and/or structure similarity with known allergens, the use of individual sera from allergic individuals rather than pooled sera is recommended. In addition to the pepsin resistance test, it is recommended that the resistance to digestion of the newly expressed proteins is evaluated using other in vitro digestibility tests mimicking physiological conditions of humans. Finally, when the recipient of the introduced gene is allergenic, in order to compare the allergenicty of the whole GM plant with that of its appropriate comparator(s), it is recommended that relevant characterised endogenous allergens are included in the comparative compositional analysis of the GM plant and its appropriate comparator(s). Proposals for the use of additional testing that may improve the weight-of-evidence approach and 1 On request of EFSA, Question No EFSA-Q-2005-125, adopted on 30 June 2010. 2 Panel members:

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The mucosal immune system: from control of inflammation to protection against infections

Cited by 23 publications

References 48 publications

Exogenous HIV-1 Nef Upsets the IFN-γ-Induced Impairment of Human Intestinal Epithelial Integrity

Exogenous HIV-1 Nef Upsets the IFN-γ-Induced Impairment of Human Intestinal Epithelial Integrity

Cationic Polypeptides Are Required for Anti-HIV-1 Activity of Human Vaginal Fluid

Scientific Opinion on the assessment of allergenicity of GM plants and microorganisms and derived food and feed

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