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.
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: The study 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 proinflammatory
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.