The involvement of neutrophils in the resistance to Leishmania major infection in susceptible but not in resistant mice

Chen, Lin; Zhang, Zhi‐Hui; Watanabe, Tadashi; Yamashita, T; Kobayakawa, Takatoshi; Kaneko, Akira; Fujiwara, Hiromi; Sendo, Fujiro

doi:10.1016/j.parint.2005.02.001

Cited by 44 publications

(52 citation statements)

References 65 publications

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“…However, there is currently a lack of consensus regarding the function of neutrophils during Leishmania promastigote infection, as these cells have been implicated in both promoting and inhibiting disease progression in different studies (14,15). Despite reporting contradictory roles for neutrophils in controlling infection, depletion studies nevertheless emphasize the importance of these cells in the early disease process of cutaneous leishmaniasis.…”

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Leishmania amazonensis Amastigotes Trigger Neutrophil Activation but Resist Neutrophil Microbicidal Mechanisms

et al. 2013

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Neutrophils are the first cells to infiltrate to the site of Leishmania promastigote infection, and these cells help to reduce parasite burden shortly after infection is initiated. Several clinical reports indicate that neutrophil recruitment is sustained over the course of leishmaniasis, and amastigote-laden neutrophils have been isolated from chronically infected patients and experimentally infected animals. The goal of this study was to compare how thioglycolate-elicited murine neutrophils respond to L. amazonensis metacyclic promastigotes and amastigotes derived from axenic cultures or from the lesions of infected mice. Neutrophils efficiently internalized both amastigote and promastigote forms of the parasite, and phagocytosis was enhanced in lipopolysaccharide (LPS)-activated neutrophils or when parasites were opsonized in serum from infected mice. Parasite uptake resulted in neutrophil activation, oxidative burst, and accelerated neutrophil death. While promastigotes triggered the release of tumor necrosis factor alpha (TNF-␣), uptake of amastigotes preferentially resulted in the secretion of interleukin-10 (IL-10) from neutrophils. Finally, the majority of promastigotes were killed by neutrophils, while axenic culture-and lesion-derived amastigotes were highly resistant to neutrophil microbicidal mechanisms. This study indicates that neutrophils exhibit distinct responses to promastigote and amastigote infection. Our findings have important implications for determining the impact of sustained neutrophil recruitment and amastigote-neutrophil interactions during the late phase of cutaneous leishmaniasis.

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Leishmania amazonensis Amastigotes Trigger Neutrophil Activation but Resist Neutrophil Microbicidal Mechanisms

et al. 2013

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“…In resistant mice, transient depletion of neutrophils has been shown to lead to an increase in the parasite load (8,9). However, neutrophil depletion in susceptible mice (BALB/c) has been shown to lead to the opposite effect, as demonstrated by an increase in parasite elimination (10,11).…”

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Neutrophils and Macrophages Cooperate in Host Resistance againstLeishmania braziliensisInfection

Novais

Santiago²,

Báfica³

et al. 2009

The Journal of Immunology

132

121

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Neutrophils play an active role in the control of infections caused by intracellular pathogens such as Leishmania. In the present study, we investigated the effect of neutrophil depletion at the time of Leishmania braziliensis infection of BALB/c mice and how neutrophils interact with the infected macrophage to promote parasite elimination. The in vivo depletion of neutrophils led to a significant increase in parasite load and enhanced the Th1-Th2 immune response in this experimental model of infection. BALB/c mice coinoculated with both parasites and live neutrophils displayed lower parasite burdens at the site of infection and in the draining lymph nodes. In vitro, we observed that live neutrophils significantly reduced the parasite load in L. braziliensis-infected murine macrophages, an effect not observed with Leishmania major. L. braziliensis elimination was dependent on the interaction between neutrophils and macrophages and was associated with TNF-α as well as superoxide production. Furthermore, cooperation between neutrophils and macrophages toward parasite elimination was also observed in experiments performed with L. braziliensis-infected human cells and, importantly, with two other New World Leishmania species. These results indicate that neutrophils play an important and previously unappreciated role in L. braziliensis infection, favoring the induction of a protective immune response.

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“…Transient depletion of neutrophils prior to infection with L. major had a significant influence on the number of parasites surviving at the site of L. major inoculation in both resistant and susceptible mice. In strains of mice resistant to infection, such as C57BL/6 and C3H/HeJ, depletion of neutrophils by the injection of a monoclonal antibody (MAb) depleting either neutrophils (NIMP-R14) or both neutrophils and eosinophils (RB6-8C5) at the time of infection and/or during the first week of infection led to an increase in the parasite load at the site of infection (21,35,49,58). These results revealed a protective role for neutrophils in L. major-resistant strains of mice, at least during the first weeks of infection.…”

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“…In addition, the absence of neutrophils during the first days of infection modified the development of the immune response to a more CD4 ϩ Th1 resistant type (less interleukin 4 and more gamma interferon [IFN-␥]) (58). However, using different strains of L. major and a MAb depleting both eosinophils and neutrophils, increased parasite numbers were measured in BALB/c mice (21,35). The difference in treatment outcomes could be related to the use of different strains of L. major and/or the use of monoclonal antibodies with different specificities (eosinophils and neutrophils versus neutrophils alone).…”

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Neutrophils Contribute to Development of a Protective Immune Response during Onset of Infection withLeishmania donovani

et al. 2008

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Neutrophils are key components of the inflammatory response and as such contribute to the killing of microorganisms. In addition, recent evidence suggests their involvement in the development of the immune response. The role of neutrophils during the first weeks post-infection with Leishmania donovani was investigated in this study. When L. donovani-infected mice were selectively depleted of neutrophils with the NIMP-R14 monoclonal antibody, a significant increase in parasite numbers was observed in the spleen and bone marrow and to a lesser extent in the liver. Increased susceptibility was associated with enhanced splenomegally, a delay in the maturation of hepatic granulomas, and a decrease in inducible nitric oxide synthase expression within granulomas. In the spleen, neutrophil depletion was associated with a significant increase in interleukin 4 (IL-4) and IL-10 levels and reduced gamma interferon secretion by CD4؉ and CD8 ؉ T cells. Increased production of serum IL-4 and IL-10 and higher levels of Leishmania-specific immunoglobulin G1 (IgG1) versus IgG2a revealed the preferential induction of Th2 responses in neutrophil-depleted mice. Altogether, these data suggest a critical role for neutrophils in the early protective response against L. donovani, both as effector cells involved in the killing of the parasites and as significant players influencing the development of a protective Th1 immune response.The best-characterized function of neutrophils or polymorphonuclear neutrophils is their preeminent role in the phagocytosis and killing of invading microorganisms via the generation of oxygen intermediates and the release of lytic enzymes stored in their granules. Neutrophils, by promoting tissue injury, also contribute to the initiation of inflammation, an essential step in the launching of immunity. In addition to their being key components of the inflammatory response, an immunoregulatory role for neutrophils during microbial infection has recently been identified via the secretion of cytokines and chemokines (reviewed in reference 16), which were shown to contribute to the recruitment and activation of antigen-presenting cells (APCs). Thus, neutrophils are now recognized as important decision shapers during the early phases of the immune response (reviewed in reference 45).The role of neutrophils in infections with Leishmania has been mainly studied using the murine model of cutaneous leishmaniasis induced by the subcutaneous injection of Leishmania major. Transient depletion of neutrophils prior to infection with L. major had a significant influence on the number of parasites surviving at the site of L. major inoculation in both resistant and susceptible mice. In strains of mice resistant to infection, such as C57BL/6 and C3H/HeJ, depletion of neutrophils by the injection of a monoclonal antibody (MAb) depleting either neutrophils (NIMP-R14) or both neutrophils and eosinophils (RB6-8C5) at the time of infection and/or during the first week of infection led to an increase in the parasite load at the site...

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The involvement of neutrophils in the resistance to Leishmania major infection in susceptible but not in resistant mice

Cited by 44 publications

References 65 publications

Leishmania amazonensis Amastigotes Trigger Neutrophil Activation but Resist Neutrophil Microbicidal Mechanisms

Leishmania amazonensis Amastigotes Trigger Neutrophil Activation but Resist Neutrophil Microbicidal Mechanisms

Neutrophils and Macrophages Cooperate in Host Resistance againstLeishmania braziliensisInfection

Neutrophils Contribute to Development of a Protective Immune Response during Onset of Infection withLeishmania donovani

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