Interleukin-17 is not required for classical macrophage activation in a pulmonary mouse model of Cryptococcus neoformans infection

Sarah E Hardison, Karen L Wozniak, Jay K Kolls, Floyd L Wormley

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Cryptococcus neoformans is an opportunistic fungal pathogen that causes disease in individuals with suppressed cell-mediated immunity. Recent studies in our laboratory have shown that increases in pulmonary Th1-type and interleukin-17A (IL-17A) cytokine production, classical macrophage activation, and sterilizing immunity are elicited in response to infection with a gamma interferon (IFN-γ)-producing C. neoformans strain, H99γ. IL-17A-treated macrophages, compared to IL-4-treated macrophages, have been demonstrated to exhibit increased microbicidal activity in vitro, a characteristic consistent with classical macrophage activation. The purpose of these studies is to determine the role of IL-17A in the induction of classically activated macrophages following infection with C. neoformans. Immunohistochemistry and real-time PCR were used to characterize the macrophage activation phenotype in lung tissues of mice treated with isotype control or anti-IL-17A antibodies and given an experimental pulmonary infection with C. neoformans strain H99γ. The pulmonary fungal burden was resolved, albeit more slowly, in mice depleted of IL-17A compared to the fungal burden in isotype control-treated mice. Nonetheless, no difference in classical macrophage activation was observed in IL-17A-depleted mice. Similarly, classical macrophage activation was evident in mice deficient in IL-17A or the IL-17 receptor A, which mediates IL-17A signaling, following pulmonary infection with wild-type C. neoformans strain H99 or H99γ. These studies suggest that IL-17A may play a role in the early immune response to C. neoformans but is not required for classical macrophage activation in mice experimentally infected with C. neoformans.

Original languageEnglish
Pages (from-to)5341-5351
Number of pages11
JournalInfection and Immunity
Volume78
Issue number12
Early online date4 Oct 2010
DOIs
Publication statusPublished - 1 Dec 2010

Fingerprint

Cryptococcus neoformans
Macrophage Activation
Interleukin-17
Lung
Infection
Macrophages
Interleukin-17 Receptors
Cellular Immunity
Interleukin-4
Interferon-gamma
Real-Time Polymerase Chain Reaction
Immunity
Immunohistochemistry
Cytokines
Phenotype
Antibodies

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Interleukin-17 is not required for classical macrophage activation in a pulmonary mouse model of Cryptococcus neoformans infection. / Hardison, Sarah E; Wozniak, Karen L; Kolls, Jay K; Wormley, Floyd L.

In: Infection and Immunity, Vol. 78, No. 12, 01.12.2010, p. 5341-5351.

Research output: Contribution to journalArticle

Hardison, Sarah E ; Wozniak, Karen L ; Kolls, Jay K ; Wormley, Floyd L. / Interleukin-17 is not required for classical macrophage activation in a pulmonary mouse model of Cryptococcus neoformans infection. In: Infection and Immunity. 2010 ; Vol. 78, No. 12. pp. 5341-5351.
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