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

Abstract

Using a pulmonary model of infection, we demonstrated previously that

Evaluation of bronchoalveolar cells in pulmonary paracoccidioidomycosis

“…The reported finding of an increased number of CD8z in PCM BAL supports the notion that MIP-1a is important in attracting and stimulating this subpopulation. A protective role for CD8z T-cells has been suggested in experimental PCM since its depletion induces a more severe and/or disseminated disease in both resistant and susceptible mice [26]. Cytotoxic CD8z T-cells represent a major defence against intracellular pathogens by the production of IFN-c and cytolytic activity, and may be involved in the clearance of P. brasiliensis cells.…”

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

“…This behavior is usually associated with efficient killing of intracellular pathogens via production of oxygen or nitrogen radicals [43] and was shown to induce preferential Th1 immunity, a fact that does not occur with susceptible animals [6,13]. In fact, the adaptative immunity of B10.A mice was shown to be mediated by CD8 ϩ T cells and anergy or deletion of the CD4 ϩ T cell subset [6,7,13].…”

“…On the contrary, A/J mice presented a regressive disease with well-organized lesions containing a low number of yeasts, positive cellular immunity, and macrophage activation, resembling the benign forms of PCM [6]. Studies on pulmonary cytokines demonstrated that both mouse strains are able to secrete proinflammatory and anti-inflammatory cytokines, but higher levels of IFN-␥, IL-5, and IL-10 were present in the lungs of susceptible mice [7,8]. Using gene knockout or cytokine-depleted mice, protective immunity to Pb infection was shown to be mediated by IFN-␥, IL-12, and TNF-␣ [9 -12], all macrophage-activating cytokines.…”

A study of neolignan compounds with biological activity against Paracoccidioides brasiliensis by using quantum chemical and chemometric methods

“…Also, the most severe forms of infection are associated with high levels of specific antibodies. 4 Several compounds are used for inhibition of the P. brasiliensis and the neolignan compounds have been used for this purpose. 5 Neolignans are organic dimers derived from oxidative coupling of allyl and propenyl phenols that occur in the Myristicaceae 6-8 and other primitive plant families.…”

“…2 Effective treatment regimens are available to control the infectious process and most patients (60-80%) develop fibrotic sequelae that may severely hamper respiratory functions and limit the patient well-being. 2 Antifungal 4 Several compounds are used for inhibition of the P. brasiliensis and the neolignan compounds have been used for this purpose. 5 Neolignans are organic dimers derived from oxidative coupling of allyl and propenyl phenols that occur in the Myristicaceae 6-8 and other primitive plant families.…”