Interactions between Neutrophils and <b><i>Leishmania braziliensis</i></b> Amastigotes Facilitate Cell Activation and Parasite Clearance

Abstract

Leishmania braziliensis and Leishmania amazonensis are both causative agents of cutaneous leishmaniasis in South America. However, patient prognosis and the host immune response differ considerably depending on the infecting parasite species. The mechanisms underlying these differences appear to be multifactorial, with both host and parasite components contributing to disease outcome. As neutrophils are a prominent component of the inflammatory infiltrate in chronic cutaneous, diffuse cutaneous and mucocutaneous lesions, we examined neutrophil activation and microbicidal activity against amastigotes of L. amazonensis and L. braziliensis. We found that murine neutrophils internalized L. braziliensis amastigotes with greater efficiency than did L. amazonensis amastigotes. Additionally, L. braziliensis infection was a potent trigger for neutrophil activation, oxidative burst, degranulation and the production of interleukin (IL)-22 and IL-10, while L. amazonensis amastigotes poorly induced these responses. Finally, neutrophils were able to kill L. braziliensis amastigotes, especially when cells were activated with phorbol myristate acetate. L. amazonensis amastigotes, however, were highly resistant to neutrophil microbicidal mechanisms. This study reveals, for the first time, differential neutrophil responsiveness to distinct species of Leishmania amastigotes and highlights the complexity of neutrophil-amastigote interactions during chronic leishmaniasis.

Infection and Activation of Human Neutrophils with Fluorescent Leishmania infantum

“…Our observation that neutrophil populations exhibit heterogeneous responses to parasites in culture is consistent with observations in vitro and in vivo that PMNs take up, and though they may kill some parasites early in infection [13], they are unable to control Leishmania infection [5,22,23,25]. Our data raise the curious possibility of “silent” parasite uptake by a neutrophil subset.…”

Intracellular Clearance by Nobel Laureates

“…Along with other NET articles published in the Journal of Innate Immunity [24][25][26] , these studies emphasize the importance of neutrophils and extracellular traps in the early immune response to an invading pathogen. Together with the other contributions in the first 2017 issue, this collection of articles covers a number of essential scientific problems within the field of innate immunity that should be of great interest to our readers.…”

Foodies of Innate Immunity

“…In this issue, Carlsen et al [7] demonstrate differential neutrophil responsiveness to distinct species of Leishmania amastigotes, the cause of cutaneous leishmaniasis in South America. Their findings suggest that different species possess specific mechanisms of resistance against neutrophil effector functions, and that this should be subject to further research.…”