© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1107738
Received for publication November 8, 2007.
Revised December 17, 2007.
Accepted for publication December 20, 2007.
Alveolar macrophages from susceptible mice are more competent than those of resistant mice to control initial Paracoccidioides brasiliensis infection
Adriana Pina *
,
Simone Bernardino *,
and
Vera L. G. Calich *
*Departamento de Imunologia do Instituto de Ciências Biomédicas and Departamento de Análises Clínicas da Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, São Paulo, Brazil
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Abstract |
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Alveolar macrophages (AM) are the first host cells to interact with Paracoccidioides brasiliensis (Pb), a primary human pathogen that causes severe pulmonary infections in Latin America. To better understand innate immunity in pulmonary paracoccidioidomycosis, we decided to study the fungicidal and secretory abilities of AM from resistant (A/J) and susceptible (B10.A) mice to infection. Untreated, IFN-
and IL-12 primed AM from B10.A and A/J mice were challenged with P. brasiliensis yeasts and cocultured for 72 h. B10.A macrophages presented an efficient fungicidal ability, were easily activated by both cytokines, produced high levels of nitric oxide (NO), IL-12, and MCP-1 associated with low amounts of IL-10 and GM-CSF. In contrast, A/J AM showed impaired cytokine activation and fungal killing, secreted high levels of IL-10 and GM-CSF but low concentrations of NO, IL-12, and MCP-1. The fungicidal ability of B10.A but not of A/J macrophages was diminished by aminoguanidine treatment, although only the neutralization of TGF-
restored the fungicidal activity of A/J cells. This pattern of macrophage activation resulted in high expression of MHC class II antigens by A/J cells, while B10.A macrophages expressed elevated levels of CD40. Unexpectedly, our results demonstrated that susceptibility to a fungal pathogen can be associated with an efficient innate immunity, while a deficient innate response can ultimately favor the development of a resistant pattern to infection. Moreover, our data suggest that different pathogen recognition receptors are used by resistant and susceptible hosts to interact with P. brasiliensis yeasts, resulting in divergent antigen presentation, acquired immunity, and disease outcomes.
Key Words:
Paracoccidioidomycosis • fungicidal activity • innate immunity • fungal infection • nitric oxide • cytokines
