Review on the Role of Host Immune Response in Protection and Immunopathogenesis during Cutaneous Leishmaniasis Infection (original) (raw)
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Immune responses during cutaneous and visceral leishmaniasis
Parasitology, 2014
SUMMARYLeishmaniaare protozoan parasites spread by a sandfly insect vector and causing a spectrum of diseases collectively known as leishmaniasis. The disease is a significant health problem in many parts of the world, resulting in an estimated 1·3 million new cases and 30 000 deaths annually. Current treatment is based on chemotherapy, which is difficult to administer, expensive and becoming ineffective in several endemic regions. To date there is no vaccine against leishmaniasis, although extensive evidence from studies in animal models indicates that solid protection can be achieved upon immunization. This review focuses on immune responses toLeishmaniain both cutaneous and visceral forms of the disease, pointing to the complexity of the immune response and to a range of evasive mechanisms utilized by the parasite to bypass those responses. The amalgam of innate and acquired immunity combined with the paucity of data on the human immune response is one of the major problems curre...
Cell biology and immunology of Leishmania
Immunological Reviews, 2011
More than 20 years ago, immunologists discovered that resistance and susceptibility to experimental infection with the intracellular protozoan Leishmania major was associated with the development of T-helper 1 (Th1)-and Th2-dominated immune responses, respectively. This infectious disease model was later used to identify and assess the role of key factors, such as interleukin-12 (IL-12) and IL-4, in Th1 and Th2 maturation. While infection by Leishmania remains a popular model for immunologists who wish to assess the role of their favorite molecule in T-cell differentiation, other investigators have tried to better understand how Leishmania interact with its insect and mammalian hosts. In this review, we discuss some of these new data with an emphasis on the early events that shape the immune response to Leishmania and on the immune evasion mechanisms that allow this parasite to avoid the development of sterilizing immunity and to secure its transmission to a new host.
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.
Cutaneous leishmaniasis: immune responses in protection and pathogenesis
Nature reviews. Immunology, 2016
Cutaneous leishmaniasis is a major public health problem and causes a range of diseases from self-healing infections to chronic disfiguring disease. Currently, there is no vaccine for leishmaniasis, and drug therapy is often ineffective. Since the discovery of CD4(+) T helper 1 (TH1) cells and TH2 cells 30 years ago, studies of cutaneous leishmaniasis in mice have answered basic immunological questions concerning the development and maintenance of CD4(+) T cell subsets. However, new strategies for controlling the human disease have not been forthcoming. Nevertheless, advances in our knowledge of the cells that participate in protection against Leishmania infection and the cells that mediate increased pathology have highlighted new approaches for vaccine development and immunotherapy. In this Review, we discuss the early events associated with infection, the CD4(+) T cells that mediate protective immunity and the pathological role that CD8(+) T cells can have in cutaneous leishmaniasis.
Cytokines in Leishmaniasis: A Complex Network of Stimulatory and Inhibitory Interactions
Immunobiology, 1993
The work of immunologists, cell biologists and parasitologists in the field of leishmaniasis has not only provided important insights into the immunopathogenesis of this disease, but also yielded fundamental contributions to our understanding of basic immunological phenomena and of host-parasite interactions. The ability of recombinant interferon-y to induce the microbicidal activity of phagocytes and the opposite effect of inhibitory cytokines was first demonstrated with Leishmania-infected macrophages. The selective development of protective and disease-mediating CD4+ T lymphocytes as well as their differential influence on the course of the disease has been long investigated in the murine Leishmania major model and now represents one of the best examples for the in vivo induction of type 1 versus type 2 T helper lymphocytes. At the same time, this model has also been extensively used for immunization studies and cytokine therapy, which shed light on the functions of cytokines in vivo as well as on the mechanism(s) of disease resistance and susceptibility. In this review we will discuss the present picture of the cytokine network in murine L. major infections. Abbreviations: APC = antigen-presenting cell; ASF = activation suppression factor; CGRP = calcitonin-gene related peptide; GM-CSF = granulocyte macrophage colonystimulating factor; gp 63 = 63 kDa surface glycoprotein of Leishmania; lFN = interferon; IL = interleukin; iNOS = inducible nitric oxide synthase; LC = Langerhans cells; L. major = Leishmania major; L-NMMA = N G monomethyl-L-arginine; LPG = lipophosphoglycan; LPS = bacterial lipopolysaccharide; mAb = monoclonal antibody; MDF = macrophage-deactivating factor; NK cells = natural killer cells; NO = nitric oxide; RNl = reactive nitrogen intermediates; ROl = reactive oxygen intermediates; scid = severe combined immunodeficiency; sIL-4R = soluble IL-4 receptor; SLA = soluble leishmanial antigen; TCR = T cell receptor; Tho (ThI, Th2) = type 0 (type 1, type 2) T helper cells; TNF-a = tumor necrosis factor-a fected BALB/c mice into protected normal or nude BALB/c mice (34, 40, 42) (R, E) • transfer of CD4+ T cells from s.c. immunized BALBI c mice into naive BALB/c mice (48) (E)
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...
International Immunopharmacology, 2008
Cellular immune responses directed against protozoan parasites are key for controlling pathogen replication and disease resolution. However, an uncontrolled, or improperly controlled, response can be deleterious to the host in terms of both allowing for the establishment of pathology, as well as less effective establishment of memory responses. Human cutaneous leishmaniasis is a disease caused by the infection with Leishmania spp. following a bite from the sandfly, the natural vector of this disease. Tens of millions worldwide are currently infected with Leishmania and no effective vaccines have been developed to date. In the face of the complexity presented by the interaction between a host (humans) with the parasite, Leishmania, and the fact that this parasite is inoculated by another complex, biologically active, vector, the sandfly, it is clearly important to study the immunoregulatory mechanisms that are induced in humans naturally infected by this parasite if we hope to develop effective vaccines and immunotherapeutic treatments in the future. Our laboratory has focused over the years on the study of the local and systemic T cell response during the first episode of cutaneous leishmaniasis suffered by individuals before they undergo antimony treatment. The goal of this review is to briefly outline our findings with hopes of putting our most recent studies concerning the dichotomy between alpha/beta TCR and gamma/delta TCR expressing, CD4-CD8-(double negative-DN) T cells in the context of a balanced immune response against Leishmania and to discuss the implications of these findings toward our understanding of human leishmaniasis.
Immune Responses in Leishmaniases: An Overview
Tropical Medicine and Infectious Disease, 2022
Leishmaniasis is a parasitic, widespread, and neglected disease that affects more than 90 countries in the world. More than 20 Leishmania species cause different forms of leishmaniasis that range in severity from cutaneous lesions to systemic infection. The diversity of leishmaniasis forms is due to the species of parasite, vector, environmental and social factors, genetic background, nutritional status, as well as immunocompetence of the host. Here, we discuss the role of the immune system, its molecules, and responses in the establishment, development, and outcome of Leishmaniasis, focusing on innate immune cells and Leishmania major interactions.
Immunopathology of leishmaniasis: an update
International journal of immunopathology and pharmacology
Leishmaniasis represents a severe, increasing, public health problem. The perspective of its control is highly dependent on research progress, on therapeutic manipulations of the immune system, and on vaccine development. There is a correlation between the clinical outcome of Leishmania infection and the cytokine response profile. While a protective immune response against Leishmania has been clearly identified to be related to the influence of a type-1 response and IFN-gamma production, the precise role of T helper (TH) 2 cytokines in non-healing infections requires further exploration. IL-4 and IL-13 (TH2 cytokines) can promote disease progression in cutaneous leishmaniasis, whereas IL-4 would appear to enhance protective type-1 responses in visceral leishmaniasis. Thus, the TH1/TH2 paradigm of resistance/susceptibility to intracellular parasites is probably an oversimplification of a more complicated network of regulatory/counter regulatory interactions. Moreover, the presence of...
Advances in leishmaniasis immunopathogenesis
Acta Medica Mediterranea, 2011
Nowadays leishmaniasis is an increasing, severe, public health problem, and its control is strictly connected to vaccine development and therapeutic manipulations of the immune system. The clinical outcome of leishmaniasis is related to cytokine response profile. Immune system type-1 response and IFN-g production provide well-known protective activity against Leishmania, whereas role of T helper (T H) 2 cytokines in non-healing infections requires further exploration. As a matter of fact, IL-4 and IL-13 (T H 2 cytokines) promote disease progression in cutaneous leishmaniasis, whereas IL-4 seems to enhance protective type-1 responses in visceral leishmaniasis. Thus, immune response to intracellular parasites should dismiss the T H 1/T H 2 paradigm of resistance/susceptibility, embracing theory of a more complicated network of regulatory/counter regulatory interactions. Moreover, the presence of antigen specific regulatory T cell subsets may provide an environment that contributes to the balance between T H 1 and T H 2 cells. Finally, the involvement of CD8 + T cells has been described, but the modality of their role and function, in this kind of infection, has not been outspreed so far.