An overview of the immunopathology of human paracoccidioidomycosis

Abstract

We review here the advances in the understanding of the immunopathology of human paracoccidioidomycosis (PCM). Its investigation must take in account the intriguing natural history of the mycosis and its agent, providing clues to the mechanisms that lead to development of disease (unbalanced host-parasite relationship?) or to the clinically silent, chronic carrier state (balanced hostparasite relationship?), in exposed people living in endemic areas. Although the literature on this subject has progressed notably, the overall picture of what are the mechanisms of susceptibility or resistance continues to be fragmentary. Major advances were seen in the description of both the cytokines/chemokines associated to the different outcomes of the hostparasite interaction, and the fungus-monocyte/macrophage interaction, and cytokines released thereof by these cells. However, relatively few studies have attempted to modify, even in vitro, the patients' unbalanced immune reactivity. Consequently, the benefits of this improved knowledge did not yet reach clinical practice. Fortunately, the previous notion of the immune system as having two nearly independent arms, the innate and adaptive immunities, leaving a large gap between them, is now being overcome.Immunologists are now trying to dissect the connections between these two arms. This will certainly lead to more productive results. Current investigations should address the innate immunity events that trigger the IL-12/IFN-c axis and confer protection against PCM in those individuals living in endemic areas, who have been infected, but did not develop the mycosis.

Dendritic cell interactions withHistoplasmaandParacoccidioides

“…90 The clinical presentation of the infection ranges from a localized and benign disease to a progressive and potentially fatal systemic infection. 91 The disease severity is dependent on the interaction between several factors including immune competence and the virulence of the infecting P. brasiliensis strain. 91 Other factors include the site of infection, age and the sex of the host.…”

“…91 The disease severity is dependent on the interaction between several factors including immune competence and the virulence of the infecting P. brasiliensis strain. 91 Other factors include the site of infection, age and the sex of the host. 92 There is a strong male predominance (13:1) of symptomatic disease that may be explained in part by the inhibition of transformation from the mycelia to yeast form in the presence of estrogens, as shown in a study by Restrepo et al 88 This phenomenon could lead to decreased fungal propagation and dissemination, allowing the immune system more time to develop an effective response to the infection.…”

“…Severe disease is associated with deficiencies in cell-mediated immunity, high antibody levels, and a predominant production of antiinflammatory type 2 cytokines. 91 Several factors influence resistance or susceptibility to infection by P. brasiliensis including the amount of antigen, the number of antigen presenting cells, and the co-stimulatory microenvironment, which help determine the immune response pathway that will be initiated. 90,94 Many studies have shown the importance of the development of an appropriate CD4 Th subset for disease resolution and others have demonstrated different disease outcomes due to a dominant Th1 or Th2 response.…”

Fatal septic shock caused by Paracoccidioides brasiliensis phylogenetic species S1 in a young immunocompetent patient: a case report

“…The severity of this case can likely be ascribed to an exacerbated host response against the pathogen, as demonstrated by the immunological analysis, which presented a remarkable cell activation profile without a satisfactory T cell regulation response 10,11 . Notably, the patient showed a diminished percentage of peripheral blood T regulatory cells in comparison with healthy individuals (CD4+CD25+Foxp3+=11.1%).…”

Paracoccidioides lutzii: estudo de alguns mecanismos de patogenicidade

“…Desta forma, abordagens imunológicas que restabeleçam a resposta imune específica protetora, como terapia adjunta, reduzindo o tempo de tratamento são necessárias com urgencia (7,62,63).…”