Eosinophils and mast cells in leishmaniasis (original) (raw)
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Immune response to Leishmania infection
Leishmania is a protozoan parasite and the causative agent of the disease leishmaniasis. Antileishmanial immune response is shown to be host genotype dependent so that some inbred strains of mouse are susceptible while others are resistant. The resistance is conferred by T-helper type-1 (Th1) cells while the susceptibility is conferred by Th2 cells. Th1 cells secrete IL-2 and IFN-γ γ γ γ γ but Th2 cells secrete IL-4, IL-5 and IL-10. It has been shown that IFN-γ γ γ γ γ activates macrophages to express iNOS2, the enzyme catalyzing the formation of nitric oxide. Nitric oxide kills the intracellular amastigotes. In contrast, Th2 immune response limits the action of Th1 functions via IL-10 and IL-4, which deactivate macrophages helping intracellular parasite growth and disease progression. Being a parasite, Leishmania ensures its own survival by modulating host immune system either by inducing immunosuppression or by promoting pro-parasitic host functions. A detailed knowledge of this hostparasite interaction would help in designing prophylactic and therapeutic strategies against this infection.
The influence of early neutrophil-Leishmania interactions on the host immune response to infection
Frontiers in Cellular and Infection Microbiology, 2012
Neutrophils are the first cells recruited to the dermal site of Leishmania infection following injection by needle or sand fly bite. The role of neutrophils in either promoting or suppressing host immunity remains controversial. We discuss the events driving neutrophil recruitment, their interaction with the parasite and apoptotic fate, and the nature of their encounters with other innate cells. We suggest that the influence of the neutrophil response on infection outcome critically depends on the timing of their recruitment and the tissue environment in which it occurs.
Neutrophils Reduce the Parasite Burden in Leishmania (Leishmania) amazonensis-Infected Macrophages
PLoS ONE, 2010
Background: Studies on the role of neutrophils in Leishmania infection were mainly performed with L. (L) major, whereas less information is available for L. (L) amazonensis. Previous results from our laboratory showed a large infiltrate of neutrophils in the site of infection in a mouse strain resistant to L. (L.) amazonensis (C3H/HePas). In contrast, the susceptible strain (BALB/c) displayed a predominance of macrophages harboring a high number of amastigotes and very few neutrophils. These findings led us to investigate the interaction of inflammatory neutrophils with L. (L.) amazonensisinfected macrophages in vitro. Methodology/Principal Findings: Mouse peritoneal macrophages infected with L. (L.) amazonensis were co-cultured with inflammatory neutrophils, and after four days, the infection was quantified microscopically. Data are representative of three experiments with similar results. The main findings were 1) intracellular parasites were efficiently destroyed in the cocultures; 2) the leishmanicidal effect was similar when cells were obtained from mouse strains resistant (C3H/HePas) or susceptible (BALB/c) to L. (L.) amazonensis; 3) parasite destruction did not require contact between infected macrophages and neutrophils; 4) tumor necrosis factor alpha (TNF-a), neutrophil elastase and platelet activating factor (PAF) were involved with the leishmanicidal activity, and 5) destruction of the parasites did not depend on generation of oxygen or nitrogen radicals, indicating that parasite clearance did not involve the classical pathway of macrophage activation by TNFa, as reported for other Leishmania species. Conclusions/Significance: The present results provide evidence that neutrophils in concert with macrophages play a previously unrecognized leishmanicidal effect on L. (L.) amazonensis. We believe these findings may help to understand the mechanisms involved in innate immunity in cutaneous infection by this Leishmania species.
The Prominent Role of Neutrophils during the Initial Phase of Infection by Leishmania Parasites
Journal of Biomedicine and Biotechnology, 2010
Neutrophils are rapidly and massively recruited to the site of Leishmania inoculation, where they phagocytose the parasites, some of which are able to survive within these first host cells. Neutrophils can thus provide a transient safe shelter for the parasites, prior to their entry into macrophages where they will replicate. In addition, neutrophils release and synthesize rapidly several factors including cytokines and chemokines. The mechanism involved in their rapid recruitment to the site of parasite inoculation, as well as the putative consequences of their massive presence on the microenvironment of the focus of infection will be discussed in the context of the development of the Leishmania-specific immune response.
Protective or Detrimental? Understanding the Role of Host Immunity in Leishmaniasis
Microorganisms, 2019
The intracellular protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis, a vector-borne disease of major public health concern, estimated to affect 12 million people worldwide. The clinical manifestations of leishmaniasis are highly variable and can range from self-healing localized cutaneous lesions to life-threatening disseminated visceral disease. Once introduced into the skin by infected sandflies, Leishmania parasites interact with a variety of immune cells, such as neutrophils, monocytes, dendritic cells (DCs), and macrophages. The resolution of infection requires a finely tuned interplay between innate and adaptive immune cells, culminating with the activation of microbicidal functions and parasite clearance within host cells. However, several factors derived from the host, insect vector, and Leishmania spp., including the presence of a double-stranded RNA virus (LRV), can modulate the host immunity and influence the disease outcome. In this re...
Cytokine: X, 2020
Leishmania are protozoan parasites that predominantly reside in myeloid cells within their mammalian hosts. Monocytes and macrophages play a central role in the pathogenesis of all forms of leishmaniasis, including cutaneous and visceral leishmaniasis. The present review will highlight the diverse roles of macrophages in leishmaniasis as initial replicative niche, antimicrobial effectors, immunoregulators and as safe hideaway for parasites persisting after clinical cure. These multiplex activities are either ascribed to defined subpopulations of macrophages (e.g., Ly6C high CCR2 + inflammatory monocytes/monocyte-derived dendritic cells) or result from different activation statuses of tissue macrophages (e.g., macrophages carrying markers of of classical [M1] or alternative activation [M2]). The latter are shaped by immune-and stromal cell-derived cytokines (e.g., IFN-γ, IL-4, IL-10, TGF-β), micro milieu factors (e.g., hypoxia, tonicity, amino acid availability), host cell-derived enzymes, secretory products and metabolites (e.g., heme oxygenase-1, arginase 1, indoleamine 2,3-dioxygenase, NOS2/NO, NOX2/ROS, lipids) as well as by parasite products (e.g., leishmanolysin/gp63, lipophosphoglycan). Exciting avenues of current research address the transcriptional, epigenetic and translational reprogramming of macrophages in a Leishmania species-and tissue context-dependent manner.
Lymphocytes influence Leishmania major pathogenesis in a strain-dependent manner
PLOS Neglected Tropical Diseases, 2019
Cutaneous leishmaniasis (CL) is the most common form of leishmaniasis and is caused by several species of Leishmania parasite. Clinical presentation of CL varies from a self-healing infection to a chronic form of the disease determined by the virulence of infecting Leishmania species and host immune responses to the parasite. Mouse models of CL show contradictory roles of lymphocytes in pathogenesis, while acquired immune responses are responsible for host protection from diseases. To reconcile the inconclusive roles of acquired immune responses in pathogenesis, we infected mice from various genetic backgrounds with two pathogenic strains of Leishmania major, Friedlin or 5ASKH, and assessed the outcome of the infections. Our findings showed that the genetic backgrounds of L. major determine the impact of lymphocytes for pathogenesis. In the absence of lymphocytes, L. major Friedlin induced the lowest inflammatory reaction and pathology at the site of infection, while 5ASKH infection induced a strong inflammatory reaction and severe pathology. Lymphocytes ameliorated 5ASKH mediated pathology, while it exacerbated pathology during Friedlin infection. Excess inflammatory reactions, like the recruitment of macrophages, neutrophils, eosinophils and production of pro-inflammatory cytokines, together with uncontrolled parasite growth in the absence of lymphocytes during 5ASKH infection may induce severe pathology development. Taken together our study provides insight into the impact of differences in the genetic background of Leishmania on CL pathogenesis.