Interleukin-12 regulation of host defenses against Coccidioides immitis

D. Mitchell Magee, Rebecca A. Cox

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

We have previously reported on the alternate regulation of gamma interferon (IFN-γ) and interleukin-4 (IL-4) in inbred mouse strains which differ in their susceptibility to Coccidioides immitis. The genetically resistant DBA/2 mice manifest a predominant T-helper 1(Th1) response, with early production of IFN-γ, whereas susceptible BALB/c mice show an early production of the Th2 cytokine IL-4. Since IL-12 is one cytokine that can act early during host defenses to promote the differentiation of cytokine production towards IFN-γ and thus may promote expression of a protective immune response, we investigated the role of IL-12 in resistance to C. immitis. Administration of recombinant IL-12 to the susceptible mouse strain before and after systemic (intraperitoneal) challenge with C. immitis significantly ameliorated the course of the disease, as measured by a reduction in the fungal load in the lungs, liver, and spleen. Analysis of the cytokine mRNA in lungs from infected BALB/c mice revealed that the protective effect of recombinant IL-12 was accompanied by a shift from a Th2 to a Th1 response. The importance of IL-12 in resistance to this fungus was further established by showing that neutralization of endogenous IL-12 in the resistant DBA/2 mouse strain led to a significant increase in the fungal burden in pulmonary and extrapulmonary tissues. These results establish that IL-12 plays a pivotal role in the host defense against systemic challenge with C. immitis.

Original languageEnglish (US)
Pages (from-to)3609-3613
Number of pages5
JournalInfection and immunity
Volume64
Issue number9
DOIs
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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