Th1 and Th17 cells regulate innate immune responses and bacterial clearance during central nervous system infection

Monica M. Holley, Tammy L Kielian

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Brain abscesses arise following parenchymal infection with pyogenic bacteria and are typified by inflammation and edema, which frequently results in a multitude of long-term health problems. The impact of adaptive immunity in shaping continued innate responses during late-stage brain abscess formation is not known but is important, because robust innate immunity is required for effective bacterial clearance. To address this issue, brain abscesses were induced in TCR αβ knockout (KO) mice, because CD4 + and NKT cells represented the most numerous T cell infiltrates. TCR αβ KO mice exhibited impaired bacterial clearance during later stages of infection, which was associated with alterations in neutrophil and macrophage recruitment, as well as perturbations in cytokine/chemokine expression. Adoptive transfer of either Th1 or Th17 cells into TCR αβ KO mice restored bacterial burdens and innate immune cell infiltrates to levels detected in wild-type animals. Interestingly, adoptively transferred Th17 cells demonstrated plasticity within the CNS compartment and induced distinct cytokine secretion profiles in abscess-associated microglia and macrophages compared with Th1 transfer. Collectively, these studies identified an amplification loop for Th1 and Th17 cells in shaping established innate responses during CNS infection to maximize bacterial clearance and differentially regulate microglial and macrophage secretory profiles.

Original languageEnglish (US)
Pages (from-to)1360-1370
Number of pages11
JournalJournal of Immunology
Volume188
Issue number3
DOIs
StatePublished - Feb 1 2012

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Th17 Cells
Central Nervous System Infections
Th1 Cells
Brain Abscess
Innate Immunity
Knockout Mice
Macrophages
Infection
Cytokines
Natural Killer T-Cells
Wild Animals
Adoptive Transfer
Neutrophil Infiltration
Microglia
Adaptive Immunity
Chemokines
Abscess
Edema
Inflammation
Bacteria

ASJC Scopus subject areas

  • Immunology

Cite this

Th1 and Th17 cells regulate innate immune responses and bacterial clearance during central nervous system infection. / Holley, Monica M.; Kielian, Tammy L.

In: Journal of Immunology, Vol. 188, No. 3, 01.02.2012, p. 1360-1370.

Research output: Contribution to journalArticle

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