The early interferon response of nasal-associated lymphoid tissue to<i>Streptococcus pyogenes</i>infection

Hyland, Kendra A.; Brennan, Robert; Olmsted, Stephen B.; Rojas, Eduardo A. Peña; Murphy, Ellen; Wang, Beinan; Cleary, P. Patrick

doi:10.1111/j.1574-695x.2009.00540.x

Cited by 24 publications

(21 citation statements)

References 43 publications

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“…Immunity was passively transferred to naive mice by CD4 + T cells only when those cells contained IL-17 + T cells. Independence of IFNγ + is consistent with the restrictive effect of IFNγ on Th17 cell differentiation and our observation that IFNγ − / − knockout mice recruit more PMN cells and macrophages into NALT and more effectively clear streptococci from this tissue than WT mice (19). We suggest that IL-17 promotes recruitment of neutrophils and macrophages, which are able to eradicate streptococci from NALT.…”

Section: Discussionsupporting

confidence: 87%

“…We observed early influxes of neutrophils and macrophages into NALT following i.n. infection of naive mice (19). Thus, amplification of TGF-β1 expression by persistent or multiple infections could be dependent on the influx of polymorphonuclear (PMN) cells and macrophages or on expansion of T cells, which can be a significant source of TGF-β1 (22).…”

Section: Discussionmentioning

confidence: 99%

“…Microarrays were used to measure cytokine RNAs as previously described (19). The reader is also referred to SI Text.…”

Section: Methodsmentioning

confidence: 99%

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Induction of TGF-β1 and TGF-β1–dependent predominant Th17 differentiation by group A streptococcal infection

Wang¹,

Dileepan²,

Briscoe³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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118

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Recurrent group A Streptococcus (GAS) tonsillitis and associated autoimmune diseases indicate that the immune response to this organism can be ineffective and pathological. TGF-β1 is recognized as an essential signal for generation of regulatory T cells (Tregs) and T helper (Th) 17 cells. Here, the impact of TGF-β1 induction on the Tcell response in mouse nasal-associated lymphoid tissue (NALT) following intranasal (i.n.) infections is investigated. ELISA and TGF-β1-luciferase reporter assays indicated that persistent infection of mouse NALT with GAS sets the stage for TGF-β1 and IL-6 production, signals required for promotion of a Th17 immune response. As predicted, IL-17, the Th17 signature cytokine, was induced in a TGF-β1 signaling-dependent manner in single-cell suspensions of both human tonsils and NALT. mice. These experiments link specific induction of TGF-β1 by a bacterial infection to an in vivo Th17 immune response and show that this cellular response is sufficient for protection against GAS. The association of a Th17 response with GAS infection reveals a potential mechanism for destructive autoimmune responses in humans.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Induction of TGF-β1 and TGF-β1–dependent predominant Th17 differentiation by group A streptococcal infection

Wang¹,

Dileepan²,

Briscoe³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

118

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“…It has been suggested that IFN-g can prevent local dissemination of GAS bacteria (68) and is indispensable for protection against a lethal skin infection in mice (69). Thus, considering the potential effect of IFN-g on innate cell activation in combination with its IgG3-inducing capabilities, it can be suggested that future vaccines against GAS should aim at inducing Th1 responses.…”

Section: Discussionmentioning

confidence: 99%

Adaptive Immunity against Streptococcus pyogenes in Adults Involves Increased IFN-γ and IgG3 Responses Compared with Children

Mortensen

Nissen

Blauenfeldt

et al. 2015

The Journal of Immunology

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Each year, millions of people are infected with Streptococcus pyogenes, leading to an estimated 500,000 annual deaths worldwide. For unknown reasons, school-aged children have substantially higher infection rates than adults. The goal for this study was to provide, to our knowledge, the first detailed characterization of the human adaptive immune response against S. pyogenes in both children and adults. We report that all adults in our study, as well as most children, showed immunity against the two conserved group A streptococci (GAS) Ags, streptococcal C5a peptidase and immunogenic secreted protein. The response primarily consisted of three subsets of Th1 T cells, in which the TNF-α+ and IL-2+TNF-α+ subsets were most frequent. Humoral immunity was dominated by IgG1 and IgG3, whereas the Th2-associated IgG4 isotype was only detected at very low amounts. IgG3 levels correlated significantly with IFN-γ, but not with IL-5, IL-13, IL-17, or TNF-α. Interestingly, children showed a similar pattern of Ag-specific cytokine release, but displayed significantly lower levels of IgG3 and IFN-γ compared with adults. Thus, human immune responses against S. pyogenes consist of a robust Th1 cellular memory response in combination with IgG1/IgG3-dominated humoral immunity that increase with age. The significance of these data regarding both the increased GAS infection rate in children and the development of protective GAS vaccines is discussed.

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“…However, mice infected via oral route, which is the most common natural infection route, are only minimally affected by the pathogen (18). Intranasal infection of mice has been used as a model for studying immunity to and pathogenesis of Group A Streptococcus (19,20). NALT is the mucosa associated lymphoid tissue in the nasal cavity that has functional similarity of Peyer's patch in the gut COX-1 is generally considered a constitutive enzyme and has been implicated in normal cellular homeostasis (22).…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Ginsan Against Vibrio vulnificus Infection

Lim

Yun

et al. 2009

J Bacteriol Virol

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Ginsan, a botanic polysaccharide extracted from Panax ginseng, has recently been reported to modulate mucosal immune response. In this study, we investigated the protective effect of Ginsan against fatal Vibrio vulnificus mucosal infection. A lethal dose of V. vulnificus (1.0 × 10 6 CFU/mouse) was nasally inoculated to mice. The bacterial count in the nasal associated lymphoid tissue (NALT) of the mouse was significantly reduced in the Ginsan-treated group. The Ginsan-treated group showed improved survival compared to the control group (100% vs 18%). To elucidate the effect of Ginsan on modulating host immune response, cytokine mRNA expressions involved in mediating inflammation were determined by semiquantitative RT-PCR in the NALTs of the infected mice. Most of the cytokine mRNAs were similarly expressed as the control group. However, COX-1 mRNA expression level was higher in Ginsan-treated group compared to the control group. The protective effect of Ginsan was antagonized by treating with a specific COX-1 inhibitor, SC-560. Thus, these data suggest that the protective effect of Ginsan against V. vulnificus infection is partly mediated by modulating COX-1 expression.

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The early interferon response of nasal-associated lymphoid tissue toStreptococcus pyogenesinfection

Cited by 24 publications

References 43 publications

Induction of TGF-β1 and TGF-β1–dependent predominant Th17 differentiation by group A streptococcal infection

Induction of TGF-β1 and TGF-β1–dependent predominant Th17 differentiation by group A streptococcal infection

Adaptive Immunity against Streptococcus pyogenes in Adults Involves Increased IFN-γ and IgG3 Responses Compared with Children

Protective Effect of Ginsan Against Vibrio vulnificus Infection

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