Interleukin-12 regulation of host defenses against Coccidioides immitis

Dewey Magee, Rebecca A. Cox

Research output: Contribution to journalArticle

74 Citations (Scopus)

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
StatePublished - 1996
Externally publishedYes

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Coccidioides
Interleukin-12
Cytokines
Inbred DBA Mouse
Interleukin-4
Lung
Interferons
Inbred Strains Mice
Interferon-gamma
Fungi
Spleen
Messenger RNA
Liver

ASJC Scopus subject areas

  • Immunology

Cite this

Interleukin-12 regulation of host defenses against Coccidioides immitis. / Magee, Dewey; Cox, Rebecca A.

In: Infection and Immunity, Vol. 64, No. 9, 1996, p. 3609-3613.

Research output: Contribution to journalArticle

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