Abstract
Different levels of resistance againstRhizopus oryzaeinfection 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 toRhizopusspecies, we used different infectious outcomes observed in experimental mucormycosis to identify the most efficient macrophage response pattern againstR.oryzae in vitroandin vivo. For this, we compared BALB/c and Swiss macrophage activity before and after intravenous or intratrachealR.oryzaeinfections. The production of hydrogen peroxide (H2O2) and nitric oxide (NO) was determined in cultures of peritoneal (PMΦ) or alveolar macrophages (AMΦ) challenged with heat-killed spores ofR.oryzae. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) were measured to confirm our findings. Naïve PMΦ from female BALB/c mice showed increased production of H2O2, TNF-α, and IL-10 in the presence of heat-killed spores ofR.oryzae. Naïve PMΦ from female Swiss mice were less responsive. Naïve AMΦ from the two strains of female mice were less reactive to heat-killed spores ofR.oryzaethan PMΦ. After 30 days ofR.oryzaeintravenous infection, lower fungal load in spleen from BALB/c mice was accompanied by higher production of H2O2by PMΦ compared with Swiss mice. In contrast, AMΦ from BALB/c mice showed higher production of NO, TNF-α, and IL-10 after 7 days of intratracheal infection. The collective findings reveal that, independent of the female mouse strain, PMΦ is more reactive againstR.oryzaeupon first contact than AMΦ. In addition, increased PMΦ production of H2O2at 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.
Funder
Fundação de Amparo à Pesquisa do Estado de São Paulo
Publisher
Public Library of Science (PLoS)