MyD88 deficiency leads to decreased NK cell gamma interferon production and T cell recruitment during chlamydia muridarum genital tract infection, but a predominant Th1 response and enhanced monocytic inflammation are associated with infection resolution

Uma M. Nagarajan, James Sikes, Daniel Prantner, Charles W. Andrews, Lauren Frazer, Anna Goodwin, Jessica Snowden, Toni Darville

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

We have previously shown that MyD88 knockout (KO) mice exhibit delayed clearance of Chlamydia muridarum genital infection compared to wild-type (WT) mice. A blunted Th1 response and ineffective suppression of the Th2 response were also observed in MyD88 KO mice. The goal of the present study was to investigate specific mechanisms whereby absence of MyD88 leads to these effects and address the compensatory mechanisms in the genital tract that ultimately clear infection in the absence of MyD88. It was observed that NK cells recruited to the genital tract in MyD88 KO mice failed to produce gamma interferon (IFN-γ) mRNA and protein. This defect was associated with decreased local production of interleukin-17 (IL-17), IL-18, and tumor necrosis factor alpha (TNF-α) but normal levels of IL-12p70. Additionally, recruitment of CD4 T cells to the genital tract was reduced in MyD88 KO mice compared to that in WT mice. Although chronic infection in MyD88 KO mice resulted in oviduct pathology comparable to that of WT mice, increased histiocytic inflammation was observed in the uterine horns. This was associated with increased CCL2 levels and recruitment of macrophages as a potential compensatory mechanism. Further deletion of TLR4-TRIF signaling in MyD88 KO mice, using TLR4/MyD88 double-KO mice, did not further compromise host defense against chlamydiae, suggesting that compensatory mechanisms are Toll-like receptor (TLR) independent. Despite some polarization toward a Th2 response, a Th1 response remained predominant in the absence of MyD88, and it provided equivalent protection against a secondary infection as observed in WT mice.

Original languageEnglish (US)
Pages (from-to)486-498
Number of pages13
JournalInfection and immunity
Volume79
Issue number1
DOIs
StatePublished - Jan 1 2011

Fingerprint

Chlamydia muridarum
Reproductive Tract Infections
Knockout Mice
Natural Killer Cells
Interferon-gamma
Inflammation
T-Lymphocytes
Infection
Interleukin-18
Oviducts
Interleukin-17
Chlamydia
Toll-Like Receptors
Coinfection
Tumor Necrosis Factor-alpha
Macrophages
Pathology
Messenger RNA

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

MyD88 deficiency leads to decreased NK cell gamma interferon production and T cell recruitment during chlamydia muridarum genital tract infection, but a predominant Th1 response and enhanced monocytic inflammation are associated with infection resolution. / Nagarajan, Uma M.; Sikes, James; Prantner, Daniel; Andrews, Charles W.; Frazer, Lauren; Goodwin, Anna; Snowden, Jessica; Darville, Toni.

In: Infection and immunity, Vol. 79, No. 1, 01.01.2011, p. 486-498.

Research output: Contribution to journalArticle

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