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TGF-β and CD23 are involved in nitric oxide production by pulmonary macrophages activated by β-glucan from Paracoccidioides brasiliensis

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Abstract

Pulmonary macrophages (PM), which are CD11b/CD18+ and CD23+, may be involved in the onset of inflammatory events caused by Paracoccidioides brasiliensis in the lungs. In the present study, we measured the nitric oxide (NO) and interleukin in PM production after intratracheal (i.t.) inoculation of an enriched β-glucan cell wall fraction from P. brasiliensis (Fraction F1). BALB/c and C57/BL6 (B6) mice were i.t. treated with Fraction F1, and their PM were restimulated in vitro with LPS and interferon-γ up to 14 days after treatment. Macrophages BALB/c mice produced less NO than PM from B6 mice. The lower NO production was caused by higher production of TGF-β by pulmonary macrophages of BALB/c and was abrogated by anti-TGF-β MoAb in vitro and in vivo. Other interleukins such as IL-10, IL-4 and a combination of IL-1, TNF-α and IL-6 were not involved in NO production induced by Fraction F1. Expression of CD11b increases and expression of CD23 decreases on PM of BALB/c mice after in vivo treatment whereas PM of B6 mice do not show a variation of their phenotype. Moreover, the ability of pulmonary macrophages to induce lymphocyte proliferation was reduced in mixed cultures of CD11b+ or CD23+ macrophages but was restored when lymphocytes were cultivated in the presence of NO inhibitor (L-NMMA). Thus, the results presented herein indicate that in BALB/c but not in B6 mice TGF-ß is strongly induced by Fraction 1 in PM in vivo and suppresses NO production. Low NO production by PM is associated with a change in CD11b/CD23 expression and with a high lymphocyte proliferative response. Thus, CD11b+/CD23+ PM modulate NO and TGF-β production in the pulmonary microenvironment.

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Acknowledgments

CNPq—Conselho Tecnológico de Pesquisa e Desenvolvimento, FAPESP—Fundação de Amparo à Pesquisa do Estado de São Paulo; Programa de Apoio a Pesquisa da Universidade de Uberaba—PAPE-UNIUBE.

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Authors and Affiliations

  1. Pro-Rectory of Research, Post-Graduation and Extension, University of Uberaba, Uberaba, Minas Gerais, 38050-500, Brazil

    Marcelo Fernandes da Silva

  2. Laboratory of Biopathology, University of Uberaba, Uberaba, Minas Gerais, Brazil

    Luiz de Pádua Queiroz Jr, Marden Estevão Mattos Jr & Marcelo Fernandes da Silva

  3. Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil

    Célio Lopes Silva

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  1. Luiz de Pádua Queiroz Jr
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Correspondence to Marcelo Fernandes da Silva.

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de Pádua Queiroz, L., Mattos, M.E., da Silva, M.F. et al. TGF-β and CD23 are involved in nitric oxide production by pulmonary macrophages activated by β-glucan from Paracoccidioides brasiliensis . Med Microbiol Immunol 199, 61–69 (2010). https://doi.org/10.1007/s00430-009-0138-1

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