Induction and expression of cell-mediated immune responses in inbred mice infected with Coccidioides immitis

Abstract

Comparisons of the course of coccidioidomycosis in two strains of inbred mice established that BALB/c mice are significantly more susceptible to pulmonary infection with Coccidioides immitis than are DBA/2 mice. The susceptibility of BALB/c mice does not reside in their inability to mount a delayed-type hypersensitivity response to C. immihis antigen. That is, BALB/c mice manifested footpad hypersensitivity to coccidioidin early during the course of disease, to a level comparable to that of DBA/2 mice. In contrast to the more resistant DBA/2 mouse strain, however, BALB/c mice developed anergy by day 15 postinfection. Suppression of the delayed-type hypersensitivity response was not specific for C. immitis antigen, as evidenced by the finding that BALB/c mice immunized with mycobacterial purified protein derivative prior to infection with C. immitis were suppressed in their footpad response to mycobacterial antigen at day 15 postinfection. Taken together, these results establish that genetically determined susceptibility to this fungus is associated with an acquired suppression of cell-mediated immune reactivity. Coccidioidomycosis is a mycotic disease caused by the diphasic fungus Coccidioides immitis. Primary infection is acquired via inhalation of mycelial-phase arthroconidia, which convert to endosporulating spherules in host tissue. Manifestations of the disease range from a benign, selflimited pulmonary infection to a severe, progressive, and often fatal mycosis involving pulmonary and extrapulmonary tissues. Host defense against C. immitis is T-cell dependent, transferable by immune T cells, independent of antibody, and correlative with delayed-type hypersensitivity (DTH) to coccidioidal antigens (1-3). Thus, in humans and experimental animals, primary self-limited disease is commonly associated with strong cell-mediated immune responses to C. immitis, and conversely, progressive coccidioidomycosis is associated with depressed cell-mediated immunity (CMI)

Importance of Interleukin-10 in Genetic Susceptibility of Mice to Coccidioides immitis

“…Not all people infected have the same risk of dissemination; progressive infection is about 100-fold more likely in Filipinos and African Americans than in Caucasians, implying that there is a genetic basis for susceptibility in people (reviewed in ref- erence 8). We found a similar variation in susceptibility to C. immitis infection among inbred strains of mice (17), a finding that was confirmed by Cox et al (3). DBA/2 (D2) is the most resistant mouse strain, and resistance is the dominant phenotype.…”

Strain Differences Influence Murine Pulmonary Responses toStachybotrys chartarum

“…There are no published data comparing the strain differences of all three of these strains to other fungi, but several earlier studies explored pairwise comparisons (57)(58)(59)(60)(61)(62)(63). Pulmonary exposure to Coccidioides immitis, Cryptococcus neoformans, and A. fumigatus shows that C57BL/ 6 mice are more sensitive to infection and inflammation and that BALB/c are more resistant (58,59,63); in contrast, we show the opposite. In the case of vaginal Candida and pulmonary C. immitis, BALB/c and C57BL/6 are both sensitive (57,(60)(61)(62).…”

The Regulation of Pulmonary Immunity

“…Lung infections with two microorganisms, Mtb and Cryptococcus neoformans (Cne), are discussed in this section as examples of infections requiring intact CMI for resolution. Animal models of chronic lung infections with several other important pathogenic organisms have been studied, including Pneumocystis carinii (Walzer, 1984;Shel-lit0 et al, 1990;Harmsen and Stankiewicz, 1990;Boylan and Current, 1992), Histoplasma capsdatum (Baughman et al, 1986;Defaveri and Graybill, 1991;Fojtasek et al, 1993;Allendoerfer et al, 1993), Blastomyces dermitiditis (Morozumi et al, 1982;Moser et al, 1988;Frey et al, 1989;Williams et al, 1994), Paracoccidiodes braziliensis (Brummer et al, 1984;Defaveri et al, 1989), Coccidiodes immitis (Cox et al, 1988), Chlamydia trachomatis and psittaci (Williams et al, 1988), Rhodococcus equi (Kanaly et al, 1993), and Mycobacterium auiumintracellulare (Takashima and Collins, 1988). Although infection with Legionella pneumophila can cause an acute pneumonia in susceptible hosts, it is a facultative intracellular bacterium; CMI is thought to be necessary for resolution of the infection.…”