Yersinia enterocolitica promotes robust mucosal inflammatory T-cell immunity in murine neonates

Andrea Echeverry, Shinobu Saijo, Kurt Schesser, Rebecca D Adkins

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Mucosal immunity to gastrointestinal pathogens in early life has been studied only slightly. Recently, we developed an infection model in murine neonates using the gastroenteric pathogen Yersinia enterocolitica. Here, we report that oral infection of neonatal mice with low doses of virulent Y. enterocolitica leads to vigorous intestinal and systemic adaptive immunity. Y. enterocolitica infection promoted the development of anti-LcrV memory serum IgG1 and IgG2a responses of comparable affinity and magnitude to adult responses. Strikingly, neonatal mesenteric lymph node CD4+ T cells produced Yersinia-specific gamma interferon (IFN-γ) and interleukin-17A (IL-17A), exceeding adult levels. The robust T- and B-cell responses elicited in neonates exposed to Y. enterocolitica were associated with long-term protection against mucosal challenge with this pathogen. Using genetically deficient mice, we found that IFN-γ and CD4+ cells, but not B cells, are critical for protection of neonates during primary Y. enterocolitica infection. In contrast, adults infected with low bacterial doses did not require either cell population for protection. CD4-deficient neonatal mice adoptively transferred with CD4 + cells from wild-type, IFN-γ-deficient, or IL-17AF-deficient mice were equally protected from infection. These data demonstrate that inflammatory CD4+ T cells are required for protection of neonatal mice and that this protection may not require CD4-derived IFN-γ, IL-17A, or IL-17F. Overall, these studies support the idea that Y. enterocolitica promotes the development of highly inflammatory mucosal responses in neonates and that intestinal T-cell function may be a key immune component in protection from gastrointestinal pathogens in early life.

Original languageEnglish
Pages (from-to)3595-3608
Number of pages14
JournalInfection and Immunity
Volume78
Issue number8
DOIs
StatePublished - Aug 1 2010

Fingerprint

Yersinia enterocolitica
Immunity
T-Lymphocytes
Cytoprotection
Interleukin-17
Yersinia Infections
B-Lymphocytes
Infection
Yersinia
Mucosal Immunity
Adaptive Immunity
Interferon-gamma
Immunoglobulin G
Lymph Nodes
Serum
Population

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Yersinia enterocolitica promotes robust mucosal inflammatory T-cell immunity in murine neonates. / Echeverry, Andrea; Saijo, Shinobu; Schesser, Kurt; Adkins, Rebecca D.

In: Infection and Immunity, Vol. 78, No. 8, 01.08.2010, p. 3595-3608.

Research output: Contribution to journalArticle

Echeverry, Andrea ; Saijo, Shinobu ; Schesser, Kurt ; Adkins, Rebecca D. / Yersinia enterocolitica promotes robust mucosal inflammatory T-cell immunity in murine neonates. In: Infection and Immunity. 2010 ; Vol. 78, No. 8. pp. 3595-3608.
@article{8a5b73ca2df042ada915e7152e8778cb,
title = "Yersinia enterocolitica promotes robust mucosal inflammatory T-cell immunity in murine neonates",
abstract = "Mucosal immunity to gastrointestinal pathogens in early life has been studied only slightly. Recently, we developed an infection model in murine neonates using the gastroenteric pathogen Yersinia enterocolitica. Here, we report that oral infection of neonatal mice with low doses of virulent Y. enterocolitica leads to vigorous intestinal and systemic adaptive immunity. Y. enterocolitica infection promoted the development of anti-LcrV memory serum IgG1 and IgG2a responses of comparable affinity and magnitude to adult responses. Strikingly, neonatal mesenteric lymph node CD4+ T cells produced Yersinia-specific gamma interferon (IFN-γ) and interleukin-17A (IL-17A), exceeding adult levels. The robust T- and B-cell responses elicited in neonates exposed to Y. enterocolitica were associated with long-term protection against mucosal challenge with this pathogen. Using genetically deficient mice, we found that IFN-γ and CD4+ cells, but not B cells, are critical for protection of neonates during primary Y. enterocolitica infection. In contrast, adults infected with low bacterial doses did not require either cell population for protection. CD4-deficient neonatal mice adoptively transferred with CD4 + cells from wild-type, IFN-γ-deficient, or IL-17AF-deficient mice were equally protected from infection. These data demonstrate that inflammatory CD4+ T cells are required for protection of neonatal mice and that this protection may not require CD4-derived IFN-γ, IL-17A, or IL-17F. Overall, these studies support the idea that Y. enterocolitica promotes the development of highly inflammatory mucosal responses in neonates and that intestinal T-cell function may be a key immune component in protection from gastrointestinal pathogens in early life.",
author = "Andrea Echeverry and Shinobu Saijo and Kurt Schesser and Adkins, {Rebecca D}",
year = "2010",
month = "8",
day = "1",
doi = "10.1128/IAI.01272-09",
language = "English",
volume = "78",
pages = "3595--3608",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "8",

}

TY - JOUR

T1 - Yersinia enterocolitica promotes robust mucosal inflammatory T-cell immunity in murine neonates

AU - Echeverry, Andrea

AU - Saijo, Shinobu

AU - Schesser, Kurt

AU - Adkins, Rebecca D

PY - 2010/8/1

Y1 - 2010/8/1

N2 - Mucosal immunity to gastrointestinal pathogens in early life has been studied only slightly. Recently, we developed an infection model in murine neonates using the gastroenteric pathogen Yersinia enterocolitica. Here, we report that oral infection of neonatal mice with low doses of virulent Y. enterocolitica leads to vigorous intestinal and systemic adaptive immunity. Y. enterocolitica infection promoted the development of anti-LcrV memory serum IgG1 and IgG2a responses of comparable affinity and magnitude to adult responses. Strikingly, neonatal mesenteric lymph node CD4+ T cells produced Yersinia-specific gamma interferon (IFN-γ) and interleukin-17A (IL-17A), exceeding adult levels. The robust T- and B-cell responses elicited in neonates exposed to Y. enterocolitica were associated with long-term protection against mucosal challenge with this pathogen. Using genetically deficient mice, we found that IFN-γ and CD4+ cells, but not B cells, are critical for protection of neonates during primary Y. enterocolitica infection. In contrast, adults infected with low bacterial doses did not require either cell population for protection. CD4-deficient neonatal mice adoptively transferred with CD4 + cells from wild-type, IFN-γ-deficient, or IL-17AF-deficient mice were equally protected from infection. These data demonstrate that inflammatory CD4+ T cells are required for protection of neonatal mice and that this protection may not require CD4-derived IFN-γ, IL-17A, or IL-17F. Overall, these studies support the idea that Y. enterocolitica promotes the development of highly inflammatory mucosal responses in neonates and that intestinal T-cell function may be a key immune component in protection from gastrointestinal pathogens in early life.

AB - Mucosal immunity to gastrointestinal pathogens in early life has been studied only slightly. Recently, we developed an infection model in murine neonates using the gastroenteric pathogen Yersinia enterocolitica. Here, we report that oral infection of neonatal mice with low doses of virulent Y. enterocolitica leads to vigorous intestinal and systemic adaptive immunity. Y. enterocolitica infection promoted the development of anti-LcrV memory serum IgG1 and IgG2a responses of comparable affinity and magnitude to adult responses. Strikingly, neonatal mesenteric lymph node CD4+ T cells produced Yersinia-specific gamma interferon (IFN-γ) and interleukin-17A (IL-17A), exceeding adult levels. The robust T- and B-cell responses elicited in neonates exposed to Y. enterocolitica were associated with long-term protection against mucosal challenge with this pathogen. Using genetically deficient mice, we found that IFN-γ and CD4+ cells, but not B cells, are critical for protection of neonates during primary Y. enterocolitica infection. In contrast, adults infected with low bacterial doses did not require either cell population for protection. CD4-deficient neonatal mice adoptively transferred with CD4 + cells from wild-type, IFN-γ-deficient, or IL-17AF-deficient mice were equally protected from infection. These data demonstrate that inflammatory CD4+ T cells are required for protection of neonatal mice and that this protection may not require CD4-derived IFN-γ, IL-17A, or IL-17F. Overall, these studies support the idea that Y. enterocolitica promotes the development of highly inflammatory mucosal responses in neonates and that intestinal T-cell function may be a key immune component in protection from gastrointestinal pathogens in early life.

UR - http://www.scopus.com/inward/record.url?scp=77955302687&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955302687&partnerID=8YFLogxK

U2 - 10.1128/IAI.01272-09

DO - 10.1128/IAI.01272-09

M3 - Article

C2 - 20515925

AN - SCOPUS:77955302687

VL - 78

SP - 3595

EP - 3608

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 8

ER -