High Levels of Interleukin-10 Impair Resistance to Pulmonary Coccidioidomycosis in Mice in Part through Control of Nitric Oxide Synthase 2 Expression

We have shown previously that there is a direct correlation between IL-10 levels and susceptibility to Coccidioides immitis peritonitis in C57BL/6 (B6), DBA/2, and BXD recombinant inbred mice. We now show that B6 mice are also more susceptible to C. immitis pneumonia and that interleukin-10 (IL-10)-...

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Bibliographic Details
Published in:Infection and Immunity 2006-06, Vol.74 (6), p.3387-3395
Main Authors: Jimenez, Maria del Pilar, Walls, Lorraine, Fierer, Joshua
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Coccidioides immitis
Coccidioidomycosis
Coccidioidomycosis - immunology
Female
Fundamental and applied biological sciences. Psychology
Fungal and Parasitic Infections
Gene Expression Regulation, Enzymologic
Guanidines - pharmacology
Human mycoses
Infectious diseases
Interleukin-10 - genetics
Interleukin-10 - physiology
Interleukin-4 - genetics
Lung Diseases, Fungal - immunology
Lysine - analogs & derivatives
Lysine - pharmacology
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Inbred DBA
Microbiology
Mycoses
Nitric Oxide Synthase Type II - genetics
RNA, Messenger - analysis
Tropical mycoses
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Summary:We have shown previously that there is a direct correlation between IL-10 levels and susceptibility to Coccidioides immitis peritonitis in C57BL/6 (B6), DBA/2, and BXD recombinant inbred mice. We now show that B6 mice are also more susceptible to C. immitis pneumonia and that interleukin-10 (IL-10)-deficient (IL-10⁻/⁻) B6 mice are more resistant to C. immitis pneumonia. In addition, we established that high levels of IL-10 are sufficient to make genetically resistant mice susceptible to both C. immitis peritonitis and pneumonia by infecting h.IL-10 transgenic mice. Infected h.IL-10 transgenic mice express lower levels of gamma interferon, IL-12 p40, and inducible nitric oxide synthetase 2 (NOS2) mRNA in their lungs, implicating inducible NOS as a defense mechanism in this disease. We treated DBA/2 mice with aminoguanidine, and they became more susceptible to C. immitis peritonitis and pneumonia. We conclude that high levels of IL-10 are both necessary and sufficient to make mice susceptible to C. immitis, regardless of the genetic background of the mice, and that IL-10 impairs resistance to C. immitis in part by suppressing NO synthesis.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.01985-05