Delayed-type hypersensitivity response in an isogenic murine model of paracoccidioidomycosis

Abstract

The specific delayed-type hypersensitivity (DTH) response was evaluated in resistant (A/SN) and susceptible (B10.A) mice intraperitoneally infected with yeasts from a virulent (Pb18) or from a non-virulent (Pb265) Paracoccidioides brasiliensis isolates. Both strains of mice were footpad challenged with homologous antigens. Pb18 infected A/SN mice developed an evident and persistent DTH response late in the course of the disease (90th day on) whereas B10.A animals mounted a discrete and ephemeral DTH response at the 14th day post-infection. A/SN mice infected with Pb265 developed cellular immune responses whereas B10.A mice were almost always anergic. Histological analysis of the footpads of infected mice at 48 hours after challenge showed a mixed infiltrate consisting of predominantly mononuclear cells. Previous infection of resistant and susceptible mice with Pb18 did not alter their DTH responses against heterologous unrelated antigens (sheep red blood cells and dinitrofluorobenzene) indicating that the observed cellular anergy was antigen-specific. When fungal related antigens (candidin and histoplasmin) were tested in resistant mice, absence of cross-reactivity was noted. Thus, specific DTH responses against P. brasiliensis depend on both the host's genetically determined resistance and the virulence of the fungal isolate.

Depletion of CD8+T Cells In Vivo Impairs Host Defense of Mice Resistant and Susceptible to Pulmonary Paracoccidioidomycosis

“…DTH reactions were always evaluated just before sacrifice of the animals used in the CFU assays by the footpad test, under previously determined conditions (17). Briefly, mice were inoculated with 25 l of Fava Netto's antigen (16) and footpad thickness was measured with a caliper (Mitutoyo Corporation, Tokyo, Japan) immediately before and 24 h after antigen inoculation.…”

Absence of Interleukin-4 Determines Less Severe Pulmonary Paracoccidioidomycosis Associated with Impaired Th2 Response

“…The DTH reactions were always evaluated just before sacrifice of the same animals used in the CFU assays by the footpad test according to previously determined conditions (19). Briefly, mice were inoculated with 25 l of Fava Netto antigen (18), and the footpad thickness was measured with a caliper (Mitutoyo Corporation, Tokyo, Japan) immediately before and 24 h after antigen inoculation.…”

Dual Role for Nitric Oxide in Paracoccidioidomycosis: Essential for Resistance, but Overproduction Associated with Susceptibility

“…We have previously shown that in susceptible (B10.A), but not in resistant (A/Sn), mice, Pb infection is accompanied by suppression of the Ab response to unrelated Ags and an impaired delayedtype hypersensitivity reaction (9,10). In the present work, we selected these two polar mouse strains to ascertain by comparison which of the macrophage-derived products could be associated with resistance or susceptibility to Pb infection.…”