Role of the lipoxin A4 receptor in the development of neutrophil extracellular traps in Leishmania infantum infection

Wei, Furong; Gong, Weiming; Wang, Junyun; Yang, Yan; Liu, Jianxiu; Wang, Yanjuan; Cao, Jianping

doi:10.1186/s13071-019-3530-8

Cited by 15 publications

(6 citation statements)

References 44 publications

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“…Previously, we mainly evaluated promastigotes and examined L. amazonensis amastigotes purified from mice cutaneous lesions [ 11 , 12 ]. Subsequently, several other groups have confirmed the release of NETs from human and murine neutrophils and the HL-60 cell line after Leishmania stimulation [ 10 , 13 , 14 , 26 , 27 ]. In this study, we extended this research by showing that L. infantum axenic amastigotes induce and are trapped by NETs, which exhibit the typical NET morphology and elastase associated with the DNA scaffold.…”

Section: Discussionmentioning

confidence: 99%

Leishmania infantum Axenic Amastigotes Induce Human Neutrophil Extracellular Traps and Resist NET-Mediated Killing

Oliveira,

Oliveira-Silva,

Linhares-Lacerda

et al. 2023

TropicalMed

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Neutrophils are multifaceted cells that, upon activation, release meshes of chromatin associated with different proteins, known as neutrophil extracellular traps (NETs). Leishmania amazonensis promastigotes and amastigotes induce NET release, and we have identified the signaling pathways involved in NET extrusion activated by promastigotes. Amastigotes maintain the infection in vertebrate hosts, and we have shown the association of NETs with amastigotes in human biopsies of cutaneous leishmaniasis. However, the interaction of amastigotes and neutrophils remains poorly understood. Our study aimed to characterize the pathways involved in the formation of NETs induced by axenic amastigotes from L. infantum, the causal agent of visceral leishmaniasis. Human neutrophils pretreated with signaling pathway inhibitors were incubated with amastigotes, and NET release was quantified in the culture supernatant. Amastigote viability was checked after incubation with NETs. We found that the release of NETs by neutrophils stimulated with these amastigotes requires the participation of elastase and peptidyl arginine deaminase and the involvement of PI3K, ROS, and calcium. Moreover, amastigotes are not susceptible to NET-mediated killing. Altogether, these findings improve our comprehension of the signaling pathways implicated in the interaction between amastigotes and human neutrophils.

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Section: Discussionmentioning

confidence: 99%

Leishmania infantum Axenic Amastigotes Induce Human Neutrophil Extracellular Traps and Resist NET-Mediated Killing

Oliveira,

Oliveira-Silva,

Linhares-Lacerda

et al. 2023

TropicalMed

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“…Third, at least in vitro , macrophages phagocytose Leishmania parasites along with the neutrophil elastase that is present onto their surface; subsequently, both the parasite and the enzyme can be found into the parasitophorous vacuole of macrophages, rendering them as neutrophil‐elastase positive cells 25 . Fourth, neutrophils release their nuclear DNA along with elastase and other antimicrobial molecules to the extracellular space forming neutrophil extracellular traps against L. infantum ; 8,26 because these traps contain DNA and elastase they are expected to be both DAPI‐ and neutrophil elastase‐positive, and to falsely increase the true number of elastase‐positive cells. In any case, the results of this study clearly show that neutrophils and their elastase are abundant, especially in the lesional skin of dogs with leishmaniosis and they participate in the immune response against the parasite.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the cutaneous inflammatory cells in dogs with leishmaniosis and in dogs without the disease that were naturally infected by Leishmania infantum (syn. L. chagasi)

Hernandez-Bures

Gillen

Apostolidis

et al. 2020

Veterinary Dermatology

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Background Canine leishmaniosis (CanL) is associated with an aberrant cutaneous immune response. Few studies have compared cutaneous immune cells among dogs with leishmaniosis or infected without leishmaniosis, and noninfected dogs. Hypothesis/Objective Evaluate the number of neutrophils, histiocytes, T lymphocytes, T‐bet‐positive, GATA3‐positive, FoxP3‐positive and interleukin (IL)‐17‐positive cells, in lesional (Group A) and normal‐looking (Group B) skin of nine dogs with stage II/III leishmaniosis; in normal‐looking PCR‐positive (Group C; n = 6) or PCR‐negative (Group D; n = 6) skin of infected dogs; and in the normal‐looking skin of 12 noninfected dogs (Group E). Methods and materials Diagnosis of CanL considered clinical signs, clinicopathological abnormalities, detection of Leishmania amastigotes in lymph nodes, and/or bone marrow and positive serological results. Paraffin‐embedded skin biopsies were processed for routine immunofluorescence and positive cells were identified using commercially available anti‐canine antibodies. Results In Group A, there was a significantly higher number of neutrophils (P < 0.001), histiocytes (P = 0.012), T lymphocytes (P = 0.011), GATA3‐positive (P = 0.02) and IL‐17A‐positive (P = 0.002) cells compared to Group E. In Group B, there was a significantly higher number of histiocytes (P = 0.02), T lymphocytes (P = 0.004), GATA3‐positive (P = 0.006) and FoxP3‐positive (P = 0.028) cells compared to Group E. There was no difference in between groups A and B and between groups C or D and E. Conclusions and clinical importance In the lesional and/or normal‐looking skin of dogs with moderate/severe CanL there is an infiltration of neutrophils, histiocytes, T lymphocytes, GATA3‐, FoxP3‐ and IL17A‐positive cells. By contrast, the number of these cells is not increased in the normal‐looking skin of infected dogs without CanL compared to the skin of noninfected dogs.

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“…For example, L. donovani infection can mediate recruitment, survival, and deactivation of neutrophils via the lipoxin A4 receptor ( 16 , 31 ). Conversely, L. infantum interaction with the lipoxin A4 receptor promoted the activation of neutrophils characterized by an increase in NET formation ( 32 ). These divergent neutrophil roles due to different Leishmania species were identified by manipulating the neutrophils in animal models by treatment with neutrophil depleting antibodies that may have certain limitations ( 17 , 18 , 31 ).…”

Section: Innate Cells and Their Role In Vlmentioning

confidence: 99%

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

et al. 2021

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Leishmaniasis is endemic to the tropical and subtropical regions of the world and is transmitted by the bite of an infected sand fly. The multifaceted interactions between Leishmania, the host innate immune cells, and the adaptive immunity determine the severity of pathogenesis and disease development. Leishmania parasites establish a chronic infection by subversion and attenuation of the microbicidal functions of phagocytic innate immune cells such as neutrophils, macrophages and dendritic cells (DCs). Other innate cells such as inflammatory monocytes, mast cells and NK cells, also contribute to resistance and/or susceptibility to Leishmania infection. In addition to the cytokine/chemokine signals from the innate immune cells, recent studies identified the subtle shifts in the metabolic pathways of the innate cells that activate distinct immune signal cascades. The nexus between metabolic pathways, epigenetic reprogramming and the immune signaling cascades that drive the divergent innate immune responses, remains to be fully understood in Leishmania pathogenesis. Further, development of safe and efficacious vaccines against Leishmaniasis requires a broader understanding of the early interactions between the parasites and innate immune cells. In this review we focus on the current understanding of the specific role of innate immune cells, the metabolomic and epigenetic reprogramming and immune regulation that occurs during visceral leishmaniasis, and the strategies used by the parasite to evade and modulate host immunity. We highlight how such pathways could be exploited in the development of safe and efficacious Leishmania vaccines.

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Role of the lipoxin A4 receptor in the development of neutrophil extracellular traps in Leishmania infantum infection

Cited by 15 publications

References 44 publications

Leishmania infantum Axenic Amastigotes Induce Human Neutrophil Extracellular Traps and Resist NET-Mediated Killing

Leishmania infantum Axenic Amastigotes Induce Human Neutrophil Extracellular Traps and Resist NET-Mediated Killing

Evaluation of the cutaneous inflammatory cells in dogs with leishmaniosis and in dogs without the disease that were naturally infected by Leishmania infantum (syn. L. chagasi)

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

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