Interferon-gamma (IFN-γ)-dependent protection and synthesis of chemoattractants for mononuclear leucocytes caused by IL-12 in the lungs of mice infected with Cryptococcus neoformans

Kazuyoshi Kawakami, M. H. Qureshi, T. Zhang, Y. Koguchi, K. Shibuya, S. Naoe, A. Saito

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

We have recently demonstrated that IL-12 induced cellular inflammatory responses consisting mainly of accumulation of mononuclear leucocytes in the lungs of mice infected with Cryptococcus neoformans and protected mice against fulminant infection. We examined the involvement of endogenously synthesized IFN-γ in such a response by investigating the effects of a neutralizing monoclonal antibody against this cytokine. The latter treatment completely abrogated the positive effects of IL-12 on survival of infected mice and prevented IL-12-induced elimination of microbials from the lungs. Histopathological examination showed that accumulation of mononuclear leucocytes in the infected lungs caused by IL-12 was clearly inhibited by anti-IFN-γ MoAb. We also examined the local production of mononuclear cell- attracting chemokines such as monocyte chemotactic protein-1 (MCP-1), regulated upon activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein1α (MIP-1α), MIP-1β and IFN-γ-inducible protein 10 (IP-10) in the lungs using a reverse transcriptase-polymerase chain reaction (RT-PCR) method. We found that these chemokines were not synthesized in the infected lungs, while IL-12 treatment markedly induced their production. Interestingly, neutralizing anti-IFN-γ MoAb strongly suppressed IL-12-induced production of these chemokines. Similar results were obtained with MCP-1 and MIP-1α when their synthesis was measured at the protein level using respective ELISA kits. Our results indicate that IFN-γ plays a central role in the protective effects of IL-12 by inducing mononuclear leucocyte-attracting chemokines and cellular inflammatory responses.

Original languageEnglish
Pages (from-to)113-122
Number of pages10
JournalClinical and Experimental Immunology
Volume117
Issue number1
DOIs
Publication statusPublished - 1999 Jul 5
Externally publishedYes

Keywords

  • Chemokines
  • Cryptococcus neoformans
  • IL-12
  • Interferon-gamma
  • Lungs

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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