Balancing immunity and pathology in visceral leishmaniasis

  title={Balancing immunity and pathology in visceral leishmaniasis},
  author={Amanda C. Stanley and Christian R. Engwerda},
  journal={Immunology and Cell Biology},
Experimental visceral leishmaniasis (VL) caused by infection with Leishmania donovani results in the development of organ‐specific immunity in the two main target tissues of infection, the spleen and the liver. The liver is the site of an acute resolving infection associated with the development of inflammatory granulomas around infected Kupffer cells, and resistance to reinfection. Paradoxically, the spleen is an initial site for the generation of cell‐mediated immune responses, but ultimately… 

Regulation of immunity during visceral Leishmania infection

A comprehensive understanding of the immune events that occur during visceral Leishmania infection is crucial for the implementation of immunotherapeutic approaches that complement the current anti-Leishmania chemotherapy and the development of effective vaccines to prevent disease.

Murine visceral leishmaniasis: IgM and polyclonal B‐cell activation lead to disease exacerbation

Polyclonal B‐cell activation, which is known to be associated with human visceral leishmaniasis, is an early and intrinsic characteristic of disease and may represent a target for therapeutic intervention.

Infection Leishmania donovani Immunity following Mediated - T Cell + Long-Term CD4 Tissue Requirements for Establishing

It is demonstrated that CD4 + T cells are required for the establishment and maintenance of antiparasitic immunity in the liver, as well as for immune surveillance and suppression of parasite outgrowth in chronically infected spleens.

Immunopathogenesis of non-healing American cutaneous leishmaniasis and progressive visceral leishmaniasis

Recent evidence from human and animal studies is summarized that reveals the mechanisms of dysregulated, hyper-responses to Leishmania braziliensis, as well as the presence of disease-promoting or the absence of protective responses to Leishesmania amazonensis and Leishmaniasis donovani.

Dynamicity of Immune Regulation during Visceral Leishmaniasis

This review focuses on the immunopathogenesis of VL by chronologically summarising the developments in the studies of the immune regulation as well as the mechanisms involved.

Galectin-1 Impairs the Generation of Anti-Parasitic Th1 Cell Responses in the Liver during Experimental Visceral Leishmaniasis

The findings provide new information on the roles of galectin-1 during parasitic infection and indicate an important role for this molecule in tissue-specific Th1 cell development, but not CD4+ T cell IL-10 production.

The Role of the Immune System in Resistance to Infection

This chapter outlines the current knowledge of the immune factors implicated in the disease and discusses the role the immune system plays in resistance to infection.

Tissue Requirements for Establishing Long-Term CD4+ T Cell–Mediated Immunity following Leishmania donovani Infection

It is demonstrated that CD4+ T cells are required for the establishment and maintenance of antiparasitic immunity in the liver, as well as for immune surveillance and suppression of parasite outgrowth in chronically infected spleens.

Treatment with IP-10 induces host-protective immune response by regulating the T regulatory cell functioning in Leishmaniadonovani-infected mice

Detailed mechanistic insight is put forward into IP-10-mediated regulation of the Treg cell functioning during experimental VL, which might be helpful in combating Leishmania-induced pathogenesis.



The immunopathology of experimental visceral leishmaniasis

Experimental murine infection with the parasites that cause human visceral leishmaniasis results in the establishment of infection in the liver, spleen, and bone marrow, and the varied roles that cytokines of the tumor necrosis factor family play in immunity to this infection are highlighted.

Tissue granuloma structure‐function in experimental visceral leishmaniasis

  • H. Murray
  • Medicine, Biology
    International journal of experimental pathology
  • 2001
In experimental visceral leishmaniasis in normal mice, resistance to Leishmania donovani, a protozoan which targets tissue macrophages, depends upon T cells, Th1 cell‐type cytokine generation and activated mononuclear phagocytes, and this structure‐function relationship, in which histologically mature granulomas provide the microenvironment for intracellular L.Donovani killing, is reviewed.

B Cell-Deficient Mice Are Highly Resistant to Leishmania donovani Infection, but Develop Neutrophil-Mediated Tissue Pathology1

An inhibitory role for B lymphocytes in resistance to L. donovani is suggested, as assessed by transfer of both normal and chronic-infection serum, Ig protects μMT mice from destructive hepatic pathology, but minimally alters their resistance compared with wild-type mice.

Intradermal Infection Model for Pathogenesis and Vaccine Studies of Murine Visceral Leishmaniasis

In vaccination experiments employing the Leishmania infantum D-13 (p80) antigen, significantly higher levels of protection were found with the intradermal murine model than were foundWith a low-dose intravenous infection model, and should prove useful for further investigation of disease pathogenesis as well as vaccine studies of visceral leishmaniasis.

Leishmania donovani Infection of a Susceptible Host Results in CD4+ T‐Cell Apoptosis and Decreased Th1 Cytokine Production

It is demonstrated that more than 40% of CD4+ T’cells from a susceptible host undergo apoptosis resulting in a significant decrease in interleukin (IL)‐2 and interferon (IFN)‐γ secretion, leaving IL‐4 secretion unaffected.

Destruction of follicular dendritic cells during chronic visceral leishmaniasis.

It is demonstrated that destruction of FDCs and a concomitant loss of GCs are associated with chronic visceral leishmaniasis, and a mechanism underlying the aberrant regulation of B cell function in murine visceral leishingmaniasis is suggested.

IL‐10 mediates susceptibility to Leishmania donovani infection

It is demonstrated for the first time that IL‐10 is a critical component of the immune response that inhibits resistance to L. donovani.

Leishmania donovani infection of bone marrow stromal macrophages selectively enhances myelopoiesis, by a mechanism involving GM-CSF and TNF-alpha.

These data are the first to directly demonstrate that intracellular parasitism of a stromal cell population may modify its capacity to regulate hematopoiesis during infectious disease.

Defective CCR7 expression on dendritic cells contributes to the development of visceral leishmaniasis

It is shown that DCs from mice with chronic Leishmania donovani infection fail to migrate from the marginal zone to the periarteriolar region of the spleen, and the immunosuppression is mediated, at least in part, through the spatial segregation of DCs and T cells.

Interleukin 12 is effective treatment for an established systemic intracellular infection: experimental visceral leishmaniasis

Results extend the antimicrobial-inducing capacity of IL-12 beyond prophylaxis by indicating that IL- 12 can exert clear-cut therapeutic activity in an established intracellular infection.