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

Abstract Different levels of resistance against Rhizopus oryzae infection have been observed between inbred (BALB/c) and outbred (Swiss) mice, with is associated with the genetic background of each mouse strain. Considering that macrophages play an important role in host resistance to Rhizopus species, we use the different infectious outcomes observed in experimental mucormycosis to identify the most efficient macrophages responses pattern against R. oryzae in vitro and in vivo . For this, we compared BALB/c and Swiss macrophage activity pre-and-post intravenous or intratracheal R. oryzae infections. Production of hydrogen peroxide (H 2 O 2 ) and nitric oxide (NO) was determined in cultures of peritoneal (PMΦ) or alveolar macrophages (AMΦ) challenged, or not, with heat-killed spores of R. oryzae . Levels of TNF-α and IL-10 were also measured to enhance our findings. Naïve PMΦ from BALB/c increased the production of H 2 O 2 , TNF-α, and IL-10 in the presence of heat-killed spores of R. oryzae , while naïve PMΦ from Swiss mice was less responsive. Naïve AMΦ from two strains of mice were less reactive to heat-killed spores of R. oryzae than PMΦ. On 30 days of R. oryzae intravenous infection, lower fungal load in BALB/c strain of mice was accompanied by higher production of H 2 O 2 by PMΦ when compared with Swiss mice. Differently, AMΦ from BALB/c mice showed higher production of NO, TNF-α, and IL-10 after 7 days of intratracheal infection and after 30 days, lower fungal load, when compared with Swiss mice. According to the set of experiments performed, our findings reveal that independently of mice strain, PMΦ is more reactive against R. oryzae in the first contact than AMΦ. In addition, increased PMΦ production of H 2 O 2 at the end of disseminated infection is related to efficient fungal clearance observed in resistant (BALB/c). Our findings provide new evidence to understand the parasite-hosts relationship in mucormycosis.