Rapid phagosome formation drives parasite control in subclinical Leishmania braziliensis infection.

INTRODUCTION

Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis displays a wide spectrum of clinical manifestations characterized by an inflammatory Th1 response that leads to the development of skin lesions. In endemic areas of L. braziliensis infection, individuals who present a delayed type of hypersensitivity reaction and/or IFN-γ production to soluble Leishmania antigen (SLA) without presenting or having a history of leishmaniasis are considered to have subclinical (SC) infection. SC subjects produce less IFN-γ and TNF-α as compared to CL subjects but control infection.

OBJECTIVE

This study proposed experiments to elucidate the involvement of phagosome formation in the control of intracellular parasites in macrophages (MØ) from SC individuals. The hypothesis of the study is that SC MØ present more quickly and effectively phagosome formation against intracellular parasites compared to CL MØ.

METHODOLOGY: Monocyte-derived MØ were infected using calcein-labeled L. braziliensis promastigotes to determine parasite death and lysosome-associated membrane protein-1 (LAMP-1) (CD107a+) expression via flow cytometry to evaluate phagosome formation. The frequency of cells containing dead parasites and vesicle formation markers was determined via flow cytometry and immunofluorescence.

RESULTS

L. braziliensis killing was observed during the initial stages of infection (2 and 4 hours), maintaining this effective control even after 48 hours of infection. SC MØ exhibit higher expression of LAMP-1 during the initial events of infection as compared with cells from CL subjects and a lower number of viable parasites during the kinetics of infection.

CONCLUSION

SC MØ can form phagosomes more quickly and for longer periods, providing effective parasite control, compared to CL MØ.