ABSTRACT
@#Cryptococcus neoformans is an encapsulated fungal pathogen that causes severe disease primarily in immunocompromised patients. Adherence and internalisation of microbial pathogens into host cells often begin with engagement of microbes to the surface receptors of host. However, the mechanisms involved remain poorly understood. In this study, we investigated the association of cell surface determinants of C. neoformans with mammalian cells. Our results showed that treatment with trypsin, but not paraformaldehyde or heat killing, could reduce host-cryptococci interaction, suggesting the involvement of cell surface proteins (CSPs) of C. neoformans in the interaction. We extended our investigations to determine the roles of CSPs during cryptococci-host cells interaction by extracting and conjugating CSPs of C. neoformans to latex beads. Conjugation of CSPs with both encapsulated and acapsular C. neoformans increased the association of latex beads with mammalian alveolar epithelial cells, alveolar macrophages and monocyte-derived macrophages. Further examination on the actin organisation of the host cells implied the involvement of actin-dependent phagocytosis in the internalisation of C. neoformans in CSP-conjugated latex beads. We hypothesised that CSPs present on the cell wall of C. neoformans mediate the adherence and actin-dependent phagocytosis of cryptococci by mammalian cells. Our results warrant further studies on the exact role of CSPs in the pathogenesis of cryptococcosis
ABSTRACT
@#Background: The cytokine cascade in the immunopathogenesis of malaria infection had been widely studied. However, their specific association with survival and severe infection remained obscure.Methods: Thestudy investigated the cytokine profiles and histopathological features of malaria in the severe infection and survival models by using male ICR mice and male Sprague Dawley rats respectively.Results: The severe model, the infected ICR mice, exhibited a high parasitemia with 100% mortality after peak parasitemia at day 5 post-infection. The survival model, the infected Sprague Dawley rats, showed mild parasitemia with full recovery by day 14 of infection. Both severe and survival models showed similar histopathological severity during peak parasitemia. The severe model produced highly elevated levels of pro-inflammatory cytokines, TNF-α and IL-1α, and low levels of the anti-inflammatory cytokine, IL-4; while the survival model showed low levels of TNF-α and IL-1α with high levels of IL-4.Conclusion: There were differences in the pathogenesis of the severe and survival models of malaria infection. These could be a basis for immunotherapy of malaria in the future