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Intranasal bacteria induce Th1 but not Treg or Th2.

ABSTRACT: Commensal microorganisms colonize the nasal mucosa without inducing inflammation. Pathogens perturbing the commensal flora often invade evading immune defenses. The different types of adaptive responses that drive the distinct behaviors of commensals and pathogens, allowing one to persist at mucosal surfaces and the other to survive within tissues, are not yet clear. In the present work we demonstrate that although crossing epithelial barriers, the commensal Lactobacillus murinus stimulates epitope-specific CD4(+) T cells in nasal-associated lymphoid tissue (NALT) less efficiently than the pathogen Streptococcus pyogenes. In NALT antigen-presenting cells other than CCR6(+) CD11c(+) dendritic cells process and present the microbial antigens. Effector/memory CD4(+) T cells generated after intranasal priming with L. murinus and S. pyogenes surprisingly express similar proinflammatory cytokines and are not CD25+/FoxP3+ T-regulatory cells when recirculating in the spleen. These findings suggest that when a commensal crosses the nasal epithelial barrier it induces a proinflammatory response similar to a pathogen but without causing disease.

SUBMITTER: Costalonga M

PROVIDER: S-EPMC4637982 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Intranasal bacteria induce Th1 but not Treg or Th2.

Costalonga M M Cleary P P PP Fischer L A LA Zhao Z Z

Mucosal immunology 20081008 1

Commensal microorganisms colonize the nasal mucosa without inducing inflammation. Pathogens perturbing the commensal flora often invade evading immune defenses. The different types of adaptive responses that drive the distinct behaviors of commensals and pathogens, allowing one to persist at mucosal surfaces and the other to survive within tissues, are not yet clear. In the present work we demonstrate that although crossing epithelial barriers, the commensal Lactobacillus murinus stimulates epit ...[more]

PMID: 19079337

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Project description:BackgroundParkinson's disease (PD) affects an estimated 7 to 10 million people worldwide, and only symptomatic treatments are presently available to relieve the consequences of brain dopaminergic neurons loss. Neuronal degeneration in PD is the consequence of neuroinflammation in turn influenced by peripheral adaptive immunity, with CD4+ T lymphocytes playing a key role. CD4+ T cells may however acquire proinflammatory phenotypes, such as T helper (Th) 1 and Th17, as well as anti-inflammatory phenotypes, such as Th2 and the T regulatory (Treg) one, and to what extent the different CD4+ T cell subsets are imbalanced and their functions dysregulated in PD remains largely an unresolved issue.MethodsWe performed two cross-sectional studies in antiparkinson drug-treated and drug-naïve PD patients, and in age- and sex-matched healthy subjects. In the first one, we examined circulating Th1, Th2, Th17, and in the second one circulating Treg. Number and frequency of CD4+ T cell subsets in peripheral blood were assessed by flow cytometry and their functions were studied in ex vivo assays. In both studies, complete clinical assessment, blood count and lineage-specific transcription factors mRNA levels in CD4+ T cells were independently assessed and thereafter compared for their consistency.ResultsPD patients have reduced circulating CD4+ T lymphocytes, due to reduced Th2, Th17, and Treg. Naïve CD4+ T cells from peripheral blood of PD patients preferentially differentiate towards the Th1 lineage. Production of interferon-? and tumor necrosis factor-? by CD4+ T cells from PD patients is increased and maintained in the presence of homologous Treg. This Th1-biased immune signature occurs in both drug-naïve patients and in patients on dopaminergic drugs, suggesting that current antiparkinson drugs do not affect peripheral adaptive immunity.ConclusionsThe complex phenotypic and functional profile of CD4+ T cell subsets in PD patients strengthen the evidence that peripheral adaptive immunity is involved in PD, and represents a target for the preclinical and clinical assessment of novel immunomodulating therapeutics.

Project description:Tuberculosis (TB) is a major health problem of global concern. The control of this disease requires appropriate preventive measures, including vaccines. In TB, T helper (Th)1 cytokines provide protection whereas Th2 and T regulatory (Treg) cytokines contribute to the pathogenesis and Th17 cytokines play a role in both protection and pathogenesis. Previous studies with Mycobacterium tuberculosis-specific proteins have identified seven low molecular weight proteins, PE35, ESXA, ESXB, Rv2346c, Rv2347c, Rv3619c, and Rv3620c, as immunodominant antigens inducing Th1-cell responses in humans following natural infection with M. tuberculosis. The aim of this study was to characterize the cytokine responses induced in mice immunized with these proteins, using various adjuvants and delivery systems, i.e. chemical adjuvants (Alum and IFA), non-pathogenic mycobacteria (M. smegmatis and M. vaccae) and a DNA vaccine plasmid (pUMVC6). The immune responses were monitored by quantifying the marker cytokines secreted by Th1 (IFN-?), Th2 (IL-5), Treg (IL-10), and Th17 (IL-17A) cells. DNA corresponding to pe35, esxa, esxb, rv2346c, rv2347c, rv3619c, and rv3620c genes were cloned into the expression vectors pGES-TH-1, pDE22 and pUMVC6 for expression in Escherichia coli, mycobacteria and eukaryotic cells, respectively. Mice were immunized with the recombinants using different adjuvants and delivery systems, and spleen cells were stimulated in vitro with peptides of immunizing proteins to investigate antigen-specific secretion of Th1 (IFN-?), Th2 (IL-5), Treg (IL-10), and Th17 (IL-17A) cytokines. The results showed that spleen cells, from mice immunized with all antigens, secreted the protective Th1 cytokine IFN-?, except ESXB, with one or more adjuvants and delivery systems. However, only Rv3619c consistently induced Th1-biased responses, without the secretion of significant concentrations of Th2, Th17 and Treg cytokines, with all adjuvants and delivery systems. Rv3619c also induced antigen-specific IgG antibodies in immunized mice.

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Intranasal bacteria induce Th1 but not Treg or Th2.

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Intranasal bacteria induce Th1 but not Treg or Th2.

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