Canine neutrophils cooperate with macrophages in the early stages of Leishmania infantum in vitro infection

Abstract

Summary Leishmania infantum is the aetiological agent of human visceral leishmaniasis and canine leishmaniasis, both systemic and potentially fatal diseases. Polymorphonuclear neutrophils (PMN) are the first cells to phagocyte this parasite at the inoculation site, but macrophages (MØ) are the definitive host cells, ensuring parasite replication. The interaction between dog MØ, PMN and L infantum promastigotes was in vitro investigated. It was observed that promastigotes establish contact with blood monocyte‐derived MØ mainly by the tip of the flagellum. These cells, that efficiently bind and internalize parasites, underwent major morphological changes, produced nitric oxide (NO) and released histone H1 in order to inactivate the parasite. Transfer of intracellular parasites from PMN to MØ was confirmed by flow cytometry, using L infantum expressing a green fluorescent protein. The interaction of MØ with L infantum‐infected PMN lead to NO production and release of extracellular traps, which may contribute to parasite containment and inactivation. This study highlights for the first time the diversity of cellular and molecular events triggered by the interaction between canine PMN and MØ, which can promote a reduction of parasite burden in the early phase of L infantum infection.

Development of Dog Immune System: From in Uterus to Elderly

“…Monocytes migrate from the bloodstream into the tissues, acquiring specific phenotypes and functional characteristics. These cells can perform diverse activities, such as phagocytosis, the release of macrophage extracellular traps (METs), antigen presentation, tissue repair, and also function as scavenger cells [5][6][7].…”

Trypanosoma brucei brucei Induces Polymorphonuclear Neutrophil Activation and Neutrophil Extracellular Traps Release

“…In this context, local pro-inflammatory responses in skin lesions in AAT, resulting in focal edema, were associated with PMN recruitment and granuloma formation surrounding T. b. brucei replication sites (10). PMN reacts against protozoan and metazoan parasites by different effector mechanisms which include the release of immunomodulatory molecules [e.g., cytokines, chemokines (CXCL1, CXCL8, CXCL10) (11,12)], phagocytosis, production of reactive oxygen species (ROS), and release of neutrophil extracellular traps (NETs) (11,13,14). So far, different parasite species were identified to induce either nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-dependent or NOX-independent NETs formation (15,16).…”

“…Zoonotic relevant euglenozoan parasites, such as Leishmania spp. and Trypanosoma cruzi, were recently described to trigger NETs release in different hosts, such as humans, mice, opossums and dogs, evidencing NETs formation as an ancient and evolutionary well-conserved innate effector mechanism among mammalian species (4,11,13,14,16,(27)(28)(29)(30). So far, data on the role of NETs against highly motile T. b. brucei trypomastigotes are entirely lacking.…”

Feline Leishmaniosis: An Emerging Public Health Problem

“…infections, allowing sandfly mouthparts to pass through the skin injecting promastigotes. After that, the immune system and, more specifically, innate immunity, such as macrophages, neutrophils, and natural killer (NK) cells, are the first mechanisms against infection [ 65 , 66 , 67 ]. The parasite has the ability to survive phagocytization by macrophages, where promastigotes develop into amastigotes [ 68 ].…”