Direct antimicrobial effects of chemokines on Cryptococcus spp, with special emphasis on a 'CXC' chemokine

Cryptococcus species are ingenious human pathogens that are widespread globally. They continue to cause over 200,000 deaths per year. Presently due to the rise in resistance and therapy failure, it is necessary to shift the focus to an alternate therapeutic strategy against this pathogen. One promising approach is to emphasize the host defense system in order to develop more precise and customized treatment strategies. In this regard, research has revealed that interferon-γ-inducible CXCL10 chemokine, amongst other chemokines spanning both CXC and CC categories, has a direct killing effect in vitro against Cryptococcus neoformans and Cryptococcus gattii, with a significantly greater microbicidal effect against the former. Moreover, when CXCL10 is used in combination with CCL5, there is a significant reduction in the survival of C. gattii at normal-serum level concentration, indicating a previously unreported synergistic effect of these two chemokines. Confocal and STED microscopic studies have demonstrated that CXCL10 has both cell wall/membrane and intracellular targets against this fungus. These findings present new possibilities for developing chemokine-derived small molecule antifungals and may represent a step forward in creating precision medicine tailored to each patient.