Is the production of reactive oxygen and nitrogen species by macrophages associated with better infectious control in female mice with experimentally disseminated and pulmonary mucormycosis?

Author(s)

dos Santos, Amanda Ribeiro ; Fraga-Silva, Thais Fernanda ; Almeida-Donanzam, Debora De Fatima ; Finatto, Angela Carolina ; Marchetti, Camila ; Andrade, Maria Izilda ; de Arruda, Olavo Speranza ; Parreira de Arruda, Maria Sueli ; Venturini, James

• Document type: Journal article
• Source: PLoS One; v. 17, n. 12, p. 17-pg., 2022-12-15.

Abstract

Different levels of resistance against Rhizopus oryzae infection have been observed between inbred (BALB/c) and outbred (Swiss) mice and are associated with the genetic background of each mouse strain. Considering that macrophages play an important role in host resistance to Rhizopus species, we used different infectious outcomes observed in experimental mucormycosis to identify the most efficient macrophage response pattern against R. oryzae in vitro and in vivo. For this, we compared BALB/c and Swiss macrophage activity before and after intravenous or intratracheal R. oryzae infections. The production of hydrogen peroxide (H2O2) and nitric oxide (NO) was determined in cultures of peritoneal (PM Phi) or alveolar macrophages (AM Phi) challenged with heat-killed spores of R. oryzae. The levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were measured to confirm our findings. Naive PM Phi from female BALB/c mice showed increased production of H2O2, TNF-alpha, and IL-10 in the presence of heat-killed spores of R. oryzae. Naive PM Phi from female Swiss mice were less responsive. Naive AM Phi from the two strains of female mice were less reactive to heat-killed spores of R. oryzae than PM Phi. After 30 days of R. oryzae intravenous infection, lower fungal load in spleen from BALB/c mice was accompanied by higher production of H2O2 by PM Phi compared with Swiss mice. In contrast, AM Phi from BALB/c mice showed higher production of NO, TNF-alpha, and IL-10 after 7 days of intratracheal infection. The collective findings reveal that, independent of the female mouse strain, PM Phi is more reactive against R. oryzae upon first contact than AM Phi. In addition, increased PM Phi production of H2O2 at the end of disseminated infection is accompanied by better fungal clearance in resistant (BALB/c) mice. Our findings further the understanding of the parasite-host relationship in mucormycosis. (AU)

• FAPESP's process: 13/15513-3 - Contribution to the study of mucormycosis: development of an experimental murine model
• Grantee: Amanda Ribeiro dos Santos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation