Subcutaneous infection of mice with Paracoccidioides brasiliensis induces a peculiar pattern of inflammatory and immune responses

It is well established that resistance or susceptibility to Paracoccidioidi s brasiliensis infection in mice is under strict host's genetic control. Mi ce from A/Sn strain inoculated by the ip route are resistant to fungal infe ction while infection induced in mice from B10.A strain results in a fatal disease. The early cellular events of infection in both strains are charact erized by a marked neutrophilic infiltration that is more prominent in B10. A mice. A peculiar characteristic of the Paracoccidioides brasiliensis-mous e model is that the subcutaneous (sc) inoculations of the fungus either in resistant (A/Sn) or susceptible (B10.A) mice is self-curing and turns mice from the B10.A strain able to express typical DTH reaction to fungal antige ns, as observed in A/Sn mice. Here we report the investigation on the early events of the inflammatory response induced by the inoculation of live fun gus into the hind footpad of A/Sn (resistant) and B10.A (susceptible) mice. The influence of neutrophils on the inflammatory response and antibody tit ers or DTH response to gp43, the major fungal antigen, was also evaluated. Results showed a different course of the inflammatory response induced by f ungal inoculation in A/Sn and B10.A mice. Neutrophil depletion before infec tion differently influenced the kinetics of the inflammatory process in bot h mice strains but did not modify the fungal load in the lesions. In neutro phil depleted mice from both strains, a decrease in DTH response and an inc rease in total antibody titers to gp43 were observed. The significant incre ase in the fungal load in lesions seen in nude mice indicates that the self -limited infection evoked by fungal inoculation into the subcutaneous tissu e is a T-cell dependent phenomenon. The implications of these observations in the pathogenesis of paracoccidioidomycosis are discussed.