Susceptibility to murine cutaneous leishmaniasis correlates with the capacity to generate interleukin 3 in response to leishmania antigen in vitro

Lelchuk, Rosalia; Graveley, R.; Liew, Foo Y.

doi:10.1016/0008-8749(88)90051-2

Cited by 35 publications

(11 citation statements)

References 28 publications

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“…Similarly, IL-3 protein has not been detected either in direct ex vivo cultures of spleen cells from long-term-infected mice (S. E. J. Cotterell, unpublished data) or in restimulation assays with leishmanial antigens (21). Hence, in contrast to the significant involvement of IL-3 in visceralizing stages of L. major infection (24), this cytokine plays a limited, if any, role in the alteration of hematopoietic activity caused by L. donovani infection. Interestingly, while the fold increase in expression of mRNA for each CSF was similar in the bone marrow and spleen, progenitor cell frequency and proliferative status was increased to a greater extent in the spleen than the bone marrow.…”

Section: Discussionmentioning

confidence: 92%

“…The "safe-target" hypothesis, where increased numbers of immature myeloid cells provide a site for rapid multiplication of amastigotes, has been frequently applied to infections with L. major (13,33). In this model, both susceptibility to infection and myelopoiesis are regulated by IL-3 and GM-CSF (17,19,24), and the parasite has a tropism for immature myeloid cells (11,33). In contrast, L. donovani infection occurs most readily in mature macrophage populations (11), IL-3 is limiting during infection (reference 21 and this report), and GM-CSF is required for resistance in the liver (35).…”

Section: Discussionmentioning

confidence: 99%

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Enhanced Hematopoietic Activity Accompanies Parasite Expansion in the Spleen and Bone Marrow of Mice Infected withLeishmania donovani

2000

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In this study, we have analyzed hematopoietic activity in the spleen, bone marrow, and blood of BALB/c and scid mice infected with Leishmania donovani. Our analysis demonstrates that infection induces a rapid but transient mobilization of progenitor cells into the circulation, associated with elevated levels of granulocyte/ macrophage colony-stimulating factor (GM-CSF) and MIP-1␣. From 14 to 28 days postinfection, when parasite expansion begins in the spleen and bone marrow, both the frequency and cell cycle activity of hematopoietic progenitors, particulary CFU-granulocyte, monocyte, are dramatically increased in these organs. This is associated with increased accumulation of mRNA for GM-CSF, M-CSF, and G-CSF, but not interleukin-3. Our data also illustrate that hematopoietic activity, as assessed by changes in the frequency of progenitor cell populations and their levels of cell cycle activity, can be regulated in both a T-cell-independent and T-cell-dependent, as well as in an organ-specific, manner. Collectively, these data add to our knowledge of the long-term changes which occur in organs in which L. donovani is able to persist.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Enhanced Hematopoietic Activity Accompanies Parasite Expansion in the Spleen and Bone Marrow of Mice Infected withLeishmania donovani

2000

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“…Concomitantly, the splenic capacity for extramedullary myelopoiesis is increased 20-to 30-fold at later time points of L. donovani infection in susceptible BALB/c mice, due to a combination of selective GM-CFU progenitor expansion and their active proliferation [18]. Interestingly, comparing L. major infection in susceptible BALB/c versus resistant CBA mice, high splenic levels of the myelopoietic growth factor IL-3 and IL-3-responsive cells are associated with disease susceptibility [19], and correlate with significantly increased numbers of CD11b Gr-1 1 myeloid cells in the bone marrow and spleen upon in vivo transfer. In the case of Plasmodium, the sustained increase in myelopoiesis is in favor of the host as it results in a nonlethal infection (P. chabaudi, P. yoelii 17x).…”

Section: Increased Rate Of Myelopoiesis During Parasitic Infectionsmentioning

confidence: 99%

Myeloid‐derived suppressor cells in parasitic infections

et al. 2010

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BelgiumMyeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that share a common property of suppressing immune responses. Several helminth and protozoan parasite species have developed efficient strategies to increase the rate of medullary or extramedullary myelopoiesis and to induce the expansion and accumulation of immature myeloid cells such as MDSC. In this review, we examine current knowledge on the factors mediating enhanced myelopoiesis and MDSC induction and recruitment during parasitic infections and how the MDSC phenotype and mechanism of immune modulation and suppression depends on the factors they encounter within the host. Finally, we place MDSC expansion in the context of the critical balance between parasite elimination and pathogenicity to the host and suggest attractive avenues for future research.Key words: Myeloid-derived suppressor cells . Myelopoiesis . Parasitic infection .T-cell suppression IntroductionParasitic infections are notoriously associated with suppression of immune responses. Populations of mature myeloid cells, such as macrophages in various activation states, are capable of displaying immunosuppressive features, and as a result play important roles in the critical balance between parasite elimination and pathogenicity to host tissues [1][2][3]. Heterogeneous populations of immature myeloid cells, characterized by the surface expression of both Gr-1 and CD11b molecules in mice and a shared potent immune-suppressing activity in vitro and in vivo, have been recognized to arise as a conserved response to various insults, including cancer, bacterial and parasitic infections. Collectively, these cells have been termed myeloid-derived suppressor cells (MDSC) [4]. A number of factors complicate the analysis of MDSC biology. First, MDSC are a heterogeneous mixture of immature myeloid cells that are in various intermediate stages of myeloid cell differentiation (reflected by expression of various levels of macrophage and DC markers such as F4/80 and CD11c, respectively, as well as MHC class II, CD80/86) and murine MDSC consist of different subpopulations with varying levels of reactivity with the Gr-1 monoclonal antibody. This Gr-1 antibody binds a common epitope on the Ly6G and Ly6C antigens [5]. Using antibodies specifically recognizing Ly6C or Ly6G, MDSC have been shown to contain at least two main subfractions: the CD11b suppressive capacity in all tumor models [7,16]. The heterogeneity and plasticity of MDSC and the lack of markers to optimally distinguish MDSC from other, more mature myeloid cell types, render T-cell anti-proliferative activity to be the ultimate defining characteristic of MDSC. Despite the above-mentioned limitations, the impact of MDSC on immune responses has made MDSC the topic of intense research. To date, most of the attention has been focused on cancer-associated MDSC, whereas relatively few studies have reported the activation, phenotype and especially the role of MDSC during parasitic infections (Table 1). In thi...

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“…The production of each of these lymphokines has been associated with susceptibility in leishmaniasis (Mirkovich et al 1986, Feng et al 1988, Griel et al 1988, Lelchuk et al 1988, Heinzel et al 1989). However, contradictory results have been reported with regard to the in vitro effects of IL-4 on macrophages.…”

Section: Il'4 Has a Dual Effect On Ifn-y Mediated Macrophage Activationmentioning

confidence: 99%

Role of Cytokines and CD4+ T‐Cell Subsets in the Regulation of Parasite Immunity and Disease

Scott

Pearce

Cheever

et al. 1989

Immunological Reviews

378

206

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CD4+ T cells have been separated into two subsets, designated TH1 and TH2, based upon the repertoire of lymphokines that they produce following stimulation. We have analyzed the role of these T-cell subsets in two chronic parasitic infections, leishmaniasis and schistosomiasis. In both diseases, we found a strong association with TH1 stimulation and protection, and TH2 stimulation and immunopathology. In addition, certain parasite antigens appeared to be strongly linked with either TH1 or TH2 cell development. This led to the establishment of protective T-cell lines and clones in a L. major model, from which we identified a new candidate antigen for vaccination against Leishmania parasites. Moreover, we show that protection against L. major infection can be significantly augmented by coadministration of IFN-gamma with antigen, a lymphokine known to inhibit TH2 cell proliferation. In S. mansoni-infected mice, animals with a patent infection exhibit an overwhelming TH2 response, while animals protectively immunized with irradiated cercariae preferentially produce IFN-gamma, a lymphokine associated with TH1 cell stimulation. In addition, we show that ablation of schistosome-induced eosinophilia by in vivo anti-IL-5 monoclonal treatment fails to reduce the protection induced by irradiated cercariae. Similarly, anti-IL-5 treatment resulted in egg-induced granulomas nearly devoid of eosinophils, but only caused a marginal reduction in granuloma size. These results demonstrate that an understanding of the factors controlling TH1 and TH2 development will significantly facilitate the identification and development of vaccines for parasitic infections.

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Susceptibility to murine cutaneous leishmaniasis correlates with the capacity to generate interleukin 3 in response to leishmania antigen in vitro

Cited by 35 publications

References 28 publications

Enhanced Hematopoietic Activity Accompanies Parasite Expansion in the Spleen and Bone Marrow of Mice Infected withLeishmania donovani

Enhanced Hematopoietic Activity Accompanies Parasite Expansion in the Spleen and Bone Marrow of Mice Infected withLeishmania donovani

Myeloid‐derived suppressor cells in parasitic infections

Role of Cytokines and CD4+ T‐Cell Subsets in the Regulation of Parasite Immunity and Disease

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