Intracellular and extracellular effector activity of mouse neutrophils in response to cutaneous and visceral Leishmania parasites

Valério-Bolas, Ana; Pereira, Maria A.; Alexandre‐Pires, Graça; Santos-Mateus, David; Rodrigues, Armanda; Rafael-Fernandes, Mariana; Gabriel, Áurea Martins; Passero, Luiz Felipe Domingues; Santos‐Gomes, Gabriela

doi:10.1016/j.cellimm.2018.11.003

Cited by 11 publications

(19 citation statements)

References 38 publications

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“…A difference between the DNA amounts released by the two L. infantum strains was also noticed although not considered significant. In line with this observation, it was recently shown that murine neutrophils exposed to L. amazonensis emitted fewer NETs than those exposed to L. shawi or L. guyanensis (Valério-Bolas et al, 2019). L. infantum also induced more NETs release than L. major in human neutrophils (Guimarães-Costa et al, 2009).…”

Section: Discussionmentioning

confidence: 58%

“…This indicated that in our experiments the parasites underwent morphological transformation within the neutrophils. Previous studies also observed “amastigotes or amastigote- like forms” within promastigote- infected neutrophils as soon as after 3 h incubation (Marques et al, 2015; Quintela-Carvalho et al, 2017; Valério-Bolas et al, 2019). In addition, we did not observe any significant differences between the strains in the different infection parameters measured at two different MOIs (10 and 0.1).…”

Section: Discussionmentioning

confidence: 80%

“…Previous studies provided evidence that either human or murine neutrophils internalize promastigotes of a range of Leishmania species including L. major (Laufs et al, 2002; Van Zandbergen et al, 2004; Peters et al, 2008; Mollinedo et al, 2010; Ricci-Azevedo et al, 2016; Ronet et al, 2018) and L. infantum (Rousseau et al, 2001; Thalhofer et al, 2011; Marques et al, 2015; Quintela-Carvalho et al, 2017; Sacramento et al, 2017; Valério-Bolas et al, 2019). Species of the Viannia subgenus internalized more parasites than those of the Leishmania subgenus ( L. infantum ; L. amazonensis ) (Valério-Bolas et al, 2019). Here we confirmed infection of human neutrophils by in vitro promastigote forms of strains of the L. major or L. infantum species.…”

Section: Discussionmentioning

confidence: 99%

“…These extracellular structures made of fiber-, web- and tube- like elements emitted by activated neutrophils are rich in histones (toxic proteins to pathogens), DNA, and granular and cytosolic proteins such as NE or MPO, and are able to entrap the parasites (Guimarães-Costa et al, 2009; Valério-Bolas et al, 2019). In case of L. infantum , it appeared that tube-like structures could allow coiling phagocytosis of promastigotes by murine neutrophils (Valério-Bolas et al, 2019), an unconventional phagocytosis mechanism also used by macrophages to internalize the parasites (Hsiao et al, 2011). L. amazonensis induced the formation of NETs by a mechanism involving surface lipophosphoglycan (LPG) and was killed by them (Guimarães-Costa et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

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Infection of Human Neutrophils With Leishmania infantum or Leishmania major Strains Triggers Activation and Differential Cytokines Release

Oualha

Barhoumi

Marzouki

et al. 2019

Front. Cell. Infect. Microbiol.

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Leishmaniases are neglected diseases, caused by intracellular protozoan parasites of the Leishmania ( L .) genus. Although the principal host cells of the parasites are macrophages, neutrophils are the first cells rapidly recruited to the site of parasites inoculation, where they play an important role in the early recognition and elimination of the parasites. The nature of early interactions between neutrophils and Leishmania could influence the outcome of infection. Herein we aimed to evaluate whether different Leishmania strains, responsible for distinct clinical manifestations, could influence ex vivo functional activity of neutrophils. Human polymorphonuclear leukocytes were isolated from 14 healthy volunteers and the ex vivo infection of these cells was done with two L. infantum and one L. major strains. Infection parameters were determined and neutrophils activation was assessed by oxidative burst, degranulation, DNA release and apoptosis; cytokine production was measured by a multiplex flow cytometry analysis. Intracellular amastigotes were rescued to determine Leishmania strains survival. The results showed that L. infantum and L. major promastigotes similarly infected the neutrophils. Oxidative burst, neutrophil elastase, myeloperoxidase activity and apoptosis were significantly increased in infected neutrophils but with no differences between strains. The L. infantum -infected neutrophils induced more DNA release than those infected by L. major . Furthermore, Leishmania strains induced high amounts of IL-8 and stimulated the production of IL-1β, TNF-α, and TGF-β by human neutrophils. We observed that only one strain promoted IL-6 release by these neutrophils. The production of TNF-α was also differently induced by the parasites strains. All these results demonstrate that L. infantum and L. major strains were able to induce globally a similar ex vivo activation and apoptosis of neutrophils; however, they differentially triggered cytokines release from these cells. In addition, rescue of intracellular parasites indicated different survival rates further emphasizing on the influence of parasite strains within a species on the fate of infection.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Infection of Human Neutrophils With Leishmania infantum or Leishmania major Strains Triggers Activation and Differential Cytokines Release

Oualha

Barhoumi

Marzouki

et al. 2019

Front. Cell. Infect. Microbiol.

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“…Once in the dermis of mammals, infective promastigotes activate the complement system, and then, the parasite first survival mechanism comes into action, inhibiting complement cascade [32, 33].…”

Section: Competence Of Innate and Acquired Immune Response Determimentioning

confidence: 99%

Cutaneous Leishmaniasis: The Complexity of Host’s Effective Immune Response against a Polymorphic Parasitic Disease

Gabriel

Valério-Bolas

Palma-Marques

et al. 2019

Journal of Immunology Research

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This review is aimed at providing a comprehensive outline of the immune response displayed against cutaneous leishmaniasis (CL), the more common zoonotic infection caused by protozoan parasites of the genus Leishmania. Although of polymorphic clinical presentation, classically CL is characterized by leishmaniotic lesions on the face and extremities of the patients, which can be ulcerative, and even after healing can lead to permanent injuries and disfigurement, affecting significantly their psychological, social, and economic well-being. According a report released by the World Health Organization, the disability-adjusted life years (DALYs) lost due to leishmaniasis are close to 2.4 million, annually there are 1.0–1.5 million new cases of CL, and a numerous population is at risk in the endemic areas. Despite its increasing worldwide incidence, it is one of the so-called neglected tropical diseases. Furthermore, this review provides an overview of the existing knowledge of the host innate and acquired immune response to cutaneous species of Leishmania. The use of animal models and of in vitro studies has improved the understanding of parasite-host interplay and the complexity of immune mechanisms involved. The importance of diagnosis accuracy associated with effective patient management in CL reduction is highlighted. However, the multiple factors involved in CL epizoology associated with the unavailability of vaccines or drugs to prevent infection make difficult to formulate an effective strategy for CL control.

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

Kupani

Pandey²,

Mehrotra

2020

Journal Cellular Physiology

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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.

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Intracellular and extracellular effector activity of mouse neutrophils in response to cutaneous and visceral Leishmania parasites

Cited by 11 publications

References 38 publications

Infection of Human Neutrophils With Leishmania infantum or Leishmania major Strains Triggers Activation and Differential Cytokines Release

Infection of Human Neutrophils With Leishmania infantum or Leishmania major Strains Triggers Activation and Differential Cytokines Release

Cutaneous Leishmaniasis: The Complexity of Host’s Effective Immune Response against a Polymorphic Parasitic Disease

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

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