Immunosuppression in Paracoccidioidomycosis: T Cell Hyporesponsiveness to TwoParacoccidioides brasiliensisGlycoproteins that Elicit Strong Humoral Immune Response

Abstract

To assess human cellular immune response to paracoccidioidomycosis (PCM), lymphocyte proliferative responses to purified antigens from Paracoccidioides brasiliensis were determined in healthy persons previously infected by the fungus (positive donors), in healthy noninfected persons (controls), and in PCM patients. Affinity-purified gp70 and gp43, the two major antigens in humoral immune responses, were used. Both induced lymphocyte proliferation (gp43 species-specific) in positive donors but not in controls; healthy persons previously infected by Histoplasma capsulatum reacted to gp70 and not to gp43. A similar cross-reactivity in antibody response to gp70 was previously reported; however, antibody response to gp43 has been considered specific. Lymphocytes from PCM patients, who, unlike positive donors, have high levels of anti-gp43 and anti-gp70 antibodies, proliferated poorly with gp70 and gp43 but better with other stimuli. This dichotomy between humoral and cellular antigen-specific responses suggests a Th2 immune response in PCM, which may be related to failure to control the infection.

Alveolar macrophages from susceptible mice are more competent than those of resistant mice to control initialParacoccidioides brasiliensisinfection

“…The juvenile or acute form of the disease affects young adults of both sexes, is usually severe, and induces profound anergy of DTH reactions. Their lymphocytes behave as Th2 cells due to the enhanced secretion of IL-4, IL-5, and IL-10 [3,4]. The most common form of PCM, the adult form, has a chronic evolution and preferentially affects male individuals.…”

An overview of the immunopathology of human paracoccidioidomycosis

“…These studies showed that the nature of the cellular immune defect was predominantly antigen-specific [21,22]. Decreased immune responses to challenges with Pb-unrelated microbial antigens were probably a consequence of the impairment of the general status of the patients, instead of an intrinsic defect of the immunity of PCM patients [14,16].…”

“…In disagreement with some studies, but in agreement with others, we observed that the majority of the patients with PCM presented overall adequate T cell responses to mitogens (and to a Pb-unrelated fungal antigen). These studies are summarized in Table 1 [9][10][11][12][13][14][15][16][21][22][23][24][25][26].…”

Vaccination with Heat Shock Protein 60 Induces a Protective Immune Response against ExperimentalParacoccidioides brasiliensisPulmonary Infection

“…Specific T-cell-mediated immune responses play a fundamental role in the resistance to P. brasiliensis. Compared to individuals with localized disease, patients with systemic PCM display several defects in cellular immunity characterized by impaired in vivo delayed type hypersensitivity reactivity, alterations in the ratio of CD4 ϩ /CD8 ϩ cells, an imbalance in cytokine levels, and a depressed in vitro T-cell proliferation to fungal antigens (2,5,6,7,11,37,38).…”