Cytokine profile and cytotoxicity in response to acute intratracheal dose of Metarhizium anisopliae in BALB/c mice

Metarhizium anisopliae has been considered neither pathogenic nor toxic to mammals. However, some recent reports demonstrate that it is capable of causing infections in mammals including humans. Therefore, there is an urgent need to investigate the nature of infections this fungus induces in these animals. We therefore investigated the immunological and cytotoxic responses to acute intratracheal dose (108 conidia/50 μl) of crude conidial suspension (CCS) of M. anisopliae (ARSEF 7487) in BALB/c mice. The secretion of proinflammatory cytokine IL-6 significantly increased at all the evaluated time points post infection. The titers of IFN-γ, TNF-α, IL-12/IL-23-total p40 and IL-12-p70 showed continuous increasing trends from 6 h post infection (h PI) onwards and increased significantly at 24 h PI. While IL-10 activity was almost constant throughout the observation period, the IL-4 activity first increased at 6 h PI, beyond which it continuously decreased at the evaluated periods of time. The lactate dehydrogenase (LDH) and total protein levels increased significantly at the evaluated h PI. Collectively, the cytokine data suggested that the activation of IL-23/Th17 pathways leading to uncontrolled Th1 type response (elevated production of TNF-α, IFN-γ and IL-6) in the early hours of infection contributed to neutrophilia and tissue damage. On the other hand significantly elevated levels of total protein, LDH and albumin indicated cytotoxicity.