Early cytokine production in pulmonary Cryptococcus neoformans infections distinguishes susceptible and resistant mice.

K. A. Hoag, N. E. Street, G. B. Huffnagle, M. F. Lipscomb

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

A murine pulmonary infection model utilizing intratracheal inoculation of Cryptococcus neoformans was used to analyze cytokines produced in response to opportunistic pathogens acquired via the respiratory tract. The specific question asked was whether early cytokine secretion in lung-associated lymph nodes (LALN) would predict whether this organism would be cleared from the lung. Lung colony-forming units (CFU) were analyzed in two strains of mice over 12 wk, and lung clearance was found to be strain dependent. C.B-17 mice reduced their lung CFU burden between day 7 and day 14 of infection, had significantly higher in lung CFU than C.B-17 mice. The capacity of cells from lungs and LALN to secrete cytokines was significantly different between the strains when assessed at day 7 and day 14 after inoculation. When compared with sensitive C57BL/6 mice 7 days after infection, resistant C.B-17 mice demonstrated (1) increased interferon-gamma secretion by LALN cells in vitro in response to media alone, heat-killed cryptococci, and the T cell mitogen concanavalin A and (2) increased interleukin (IL)-2 secretion by both LALN and lung cells in response to concanavalin A. IL-4 and IL-10 were comparable or undetectable in both mouse strains, whereas IL-5 was significantly higher in all lung cell cultures of C57BL/6 mice. Thus, an early regional Th1 immune response in C.B-17 mice correlated with resistance to the organism, whereas the absence of this response in C57BL/6 mice correlated with susceptibility.

Original languageEnglish (US)
Pages (from-to)487-495
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume13
Issue number4
DOIs
StatePublished - Oct 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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