Neutrophils and Visceral Leishmaniasis: Impact on innate immune response and cross‐talks with macrophages and dendritic cells

Abstract

Neutrophils with their array of microbicidal activities are the first innate immune cells to guard against infection. They are also most crucial for the host's initial defense against Leishmania parasites which cause clinically diverse diseases ranging from self‐healing cutaneous leishmaniasis (CL) to a more severe visceral form, visceral leishmaniasis (VL). Neutrophils are recruited in large numbers at the infection site after bite of sandfly, which is the vector for the disease. The initial interaction of neutrophils with the parasites may modulate the subsequent innate and adaptive immune responses and hence affect the disease outcome. The purpose of this review is to comprehensively appraise the role of neutrophils during the early stages of Leishmania infection with a focus on the visceral form of the disease. In the past decade, new insights regarding the role of neutrophils in VL have surfaced which have been extensively elaborated in the present review. In addition, since much of the information regarding neutrophil–Leishmania early interaction has accumulated through studies on mouse models of CL, these studies are also revisited. We begin by reviewing the factors which drive the recruitment of neutrophils at the site of injection by the sandfly. We then discuss the studies delineating the molecular mechanisms involved in the uptake of the Leishmania parasite by neutrophils and how the parasite subverts their microbicidal functions. In the end, the interaction of infected neutrophils with macrophages and dendritic cells is summarized.

Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm

“…Cytokine storm is likely to occur when excess inflammatory cells, such as monocytes or neutrophils, infiltrate into the tissues, resulting in cytokine-induced necrosis. This excessive production of cytokines followed by the infiltration of inflammatory cells plays a critical role in the disease progression [ 43 , 56 , 57 , 58 , 59 ].…”

Determinants of Innate Immunity in Visceral Leishmaniasis and Their Implication in Vaccine Development

“…The species of Leishmania parasites, the host genetic background, and the apoptotic or necrotic nature of the neutrophils determine parasite transfer from neutrophils to macrophages, and the subsequent outcome of their interaction with macrophages ( 23 , 37 ). The crosstalk between neutrophils and macrophages/DCs in VL remains to be studied ( 41 ), although it is known that when human macrophages are co-cultured with neutrophils previously infected with L. infantum in the presence of salivary gland sonicate (SGS), they acquired significantly more parasites from neutrophils. These macrophages also produced more TGF‐β and prostaglandin E2 (PGE2), suggesting the importance of neutrophil-macrophage crosstalk ( 42 ).…”

“…Parasitized neutrophils may facilitate the uptake by DCs via the expression of apoptotic markers that lead to decreased DC activation and impaired cross-presentation for CD8+ T cell activation. Although CD11b on neutrophils may interact with DC‐SIGN of DCs and induce secretion of TNF‐α, such interaction remains to be demonstrated in VL ( 41 ). A predominant immunoregulatory role for neutrophils in regulating DC functions and subsequent T cell differentiation via DCs during Leishmania infection has also been reported ( 16 , 41 ).…”

“…Although CD11b on neutrophils may interact with DC‐SIGN of DCs and induce secretion of TNF‐α, such interaction remains to be demonstrated in VL ( 41 ). A predominant immunoregulatory role for neutrophils in regulating DC functions and subsequent T cell differentiation via DCs during Leishmania infection has also been reported ( 16 , 41 ). The role of alarmins released during degranulation of neutrophils and their role in altering DC functions remains to be studied in VL ( 43 ).…”

Polyamine Metabolism in Leishmania Parasites: A Promising Therapeutic Target

“…Transmission to the mammalian host occurs when an infected sand fly takes a bloodmeal. Parasites are phagocytosed by neutrophils, macrophages, or other antigen-presenting cells, although macrophages are the ultimate host cell [ 6 , 7 , 8 ]. Phagosomes containing internalized parasites merge with lysosomes to form phagolysosomes.…”