Human Monocyte/Macrophage Fungicidal Activity of GM-CSF Against Paracoccidioides brasiliensis Depends on ROS

João Paulo Martins do Carmo
2018 Cohesive Journal of Microbiology & Infectious Disease  
The ability of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to activate human monocytes/macrophages for virulent Paracoccidioides brasiliensis killing was evaluated. Peripheral blood monocytes (MO) and monocyte-derived macrophages (M∅) were activated with different concentrations of GM-CSF. Afterwards, cells were challenged with P. brasiliensis strain 18 (Pb18) and the fungicidal activity was evaluated, plating and counting the Colony Forming Units (CFU) after 10
more » ... its (CFU) after 10 days. GM-CSF activated MO and M∅ for P. brasiliensis killling in a concentration-dependent manner. There was an association between this fungicidal activity and the high levels of H 2 O 2 release by the activated cells. Moreover, the killing effect was inhibited by Catalase (CAT), confirming the role of H 2 O 2 in this process. On the other hand, L-Monomethyl-Arginine (L-NMMA) had no effect on fungicidal activity, showing that nitric oxide (NO) is not involved in killing by human cells against P. brasiliensis. Based on these data, the role of GM-CSFactivated human cells in the innate defense mechanisms against P. brasiliensis is discussed. Enhancement of the microbicidal activity of MO by GM-CSF was shown in vitro against Candida albicans [17], Aspergillus fumigates [18,19], Histoplasma capsulatum [20,21], Cryptococcus neoformans [22], Trypanosoma cruzi [23], Mycobacterium avium [24], M. lepraemurium [25] and M. avium-intracellulare Complex (MAC) [26] . Therefore, we propose that MO/macrophage activation by GM-CSF might be necessary for P. brasiliensis killing. Thus, the aim of this work was to study: A. The role of GM-CSF on human MO/macrophage fungicidal activity against a virulent strain of P. brasiliensis (Pb18); B. The involvement of reactive oxygen and nitrogen intermediates in the killing of Pb18 by GM-CSF-activated MO/ macrophages.
doi:10.31031/cjmi.2018.01.000511 fatcat:fqhvgtwpefghfajzattk6xwxe4