Cryptococcal encephalitis in thermally injured mice is accelerated by type 2 T-cell responses

Katsunori Furukawa, Makiko Kobayashi, Hidetaka Sasaki, David N. Herndon, Richard B. Pollard, Fujio Suzuki

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Objective: To explore the pathogenic role of burn-associated type 2 T-cell responses on the development of cryptococcal encephalitis in mice with severe thermal injuries. Design: Experimental Cryptococcus neoformans infection in normal mice was compared with that in thermally injured mice (TI mice), normal mice heated with a mixture of interleukin (IL)-4 and IL-10, or normal mice inoculated with burn-associated type 2 T cells. Setting: University research laboratory. Subjects: Male BALB/c mice, 8 to 10 wks of age. Interventions: We prepared four groups of mice as follows: a) normal mice, b) TI mice, c) normal mice treated with the IL-4/IL-10 mixture, and d) normal mice inoculated with burn-associated type 2 T cells. These groups of mice were anesthetized and exposed to 1 x 106 cells/mouse of C. neoformans intratracheally. Cryptococcal growth in brains and lungs in normal mice were compared with those of the other three groups. Also, cytokine-producing profiles of T lymphocytes from brains of both normal mice and TI mice were determined. Measurements and Main Results: Compared with normal mice, TI mice were susceptible to C. neoformans infection. At the maximum (15 days after infection), numbers of C. neoformans organisms in brains of TI mice were 103 times higher than those of the pathogen in brains of normal mice. After stimulation with anti-CD3 monoclonal antibody, IL-4 (but not interferon gamma) was produced in cultures of T lymphocytes from brains of TI mice 15 days after the infection, whereas the same cell preparation from normal mice produced interferon gamma (but not IL-4). TI mice and mice that were treated with a IL-4/IL-10 mixture or inoculated with burn-associated type 2 T cells were equally susceptible to the cryptococcal infection. Conclusions: Burn-associated type 2 T cells or their cytokine products play a key role in the severity of cryptococcal encephalitis that develops in TI mice.

Original languageEnglish (US)
Pages (from-to)1419-1424
Number of pages6
JournalCritical care medicine
Volume30
Issue number7
DOIs
StatePublished - Jan 1 2002

Keywords

  • Brain lymphocytes
  • Cryptococcal encephalitis
  • Thermal injury
  • Type 2 T cells
  • Type 2 cytokines

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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