The murine model of infection with Leishmania major and its importance for the deciphering of mechanisms underlying differences in Th cell differentiation in mice from different genetic backgrounds

Gumy, Alain; Louis, Jacques; Launois, Pascal

doi:10.1016/j.ijpara.2003.11.021

Cited by 77 publications

(53 citation statements)

References 122 publications

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“…First, we described that purified B cells stimulated in vitro with L. major secrete IL-10. Moreover, IL-10 expression is detected in purified CD19 + cells from draining LNs in susceptible but not in resistant mice in the first days postinfection, a window of time particularly important for Th differentiation (15). Furthermore, in contrast to the effect of adoptive transfer of B cells from BALB/c mice into BALB/c mMT mice prior to infection with L. major LV39 (20), transfer of B cells from IL-10 2/2 BALB/c mice into BALB/c mMT mice restore neither disease progression nor Th2 cell development in these otherwise resistant mice.…”

Section: Discussionmentioning

confidence: 99%

“…Studies in vivo, using the murine model of infection with L. major, have established that resistance and susceptibility to infection with this protozoan parasite are correlated with the activation of parasite-reactive CD4 + Th1 or Th2 cells, respectively (15). IL-4 has been shown for a long time to play a predominant role in directing the functional differentiation of Leishmaniareactive CD4 + Th2 T cells observed in susceptible BALB/c mice postinfection with L. major (16).…”

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confidence: 99%

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Regulatory B Cells Shape the Development of Th2 Immune Responses in BALB/c Mice Infected with Leishmania major Through IL-10 Production

Ronet

Torre

Revaz-Breton

et al. 2009

The Journal of Immunology

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Recent evidence indicates that B cells are required for susceptibility to infection with Leishmania major in BALB/c mice. In this study, we analyzed the role of the IL-10 produced by B cells in this process. We showed that B cells purified from the spleen of BALB/c mice produced IL-10 in response to stimulation with L. major in vitro. In vivo, early IL-10 mRNA expression is detected after L. major infection in B cells from draining lymph nodes of susceptible BALB/c, but not of resistant C57BL/6 mice. Although adoptive transfer of naive wild-type B cells prior to infection in B cell-deficient BALB/c mice restored Th2 cell development and susceptibility to infection with L. major of these otherwise resistant mice, adoptive transfer of IL-10−/− B cells mice did not. B cells stimulated by L. major, following in vitro or in vivo encounter, express the CD1d and CD5 molecules and the IL-10 produced by these cells downregulate IL-12 production by L. major-stimulated dendritic cells. These observations indicate that IL-10 secreting B cells are phenotypically and functionally regulatory B cells. Altogether these results demonstrate that the IL-10 produced by regulatory CD1d+ CD5+ B cells in response to L. major is critical for Th2 cell development in BALB/c mice.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Regulatory B Cells Shape the Development of Th2 Immune Responses in BALB/c Mice Infected with Leishmania major Through IL-10 Production

Ronet

Torre

Revaz-Breton

et al. 2009

The Journal of Immunology

Self Cite

139

128

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“…Extensive experimental studies have established that an effective immunity against Leishmania relies on the differentiation of CD4 ϩ T cells toward a Th1 response (68,69). Conversely, genetic or acquired deficiencies in cytokines like IL-12, IFN-␥ and TNF-␣, receptors like IL-12R and IFN-␥R, and costimulatory molecules like CD40/CD40L lead to susceptibility (70).…”

Section: Discussionmentioning

confidence: 99%

IL-10- and TGF-β-Mediated Susceptibility in Kala-azar and Post-kala-azar Dermal Leishmaniasis: The Significance of Amphotericin B in the Control of Leishmania donovani Infection in India

Saha

Mondal

Ravindran

et al. 2007

The Journal of Immunology

146

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Visceral leishmaniasis (VL) or kala-azar is known to be associated with a mixed Th1-Th2 response, and effective host defense requires the induction of IFN-γ and IL-12. We address the role of the differential decline of IL-10 and TGF-β in response to sodium antimony gluconate (SAG) and amphotericin B (AmB), the therapeutic success of SAG and AmB in Indian VL, and the significance of IL-10 and TGF-β in the development and progression of post-kazla-azar dermal leishmaniasis (PKDL). In the active disease, PBMC from VL patients showed suppressed Ag-specific lymphoproliferation, IFN-γ and IL-12 production, and elevation of IL-10 and TGF-β. Cure corresponded with an elevation in IFN-γ and IL-12 production and down-regulation of IL-10 and TGF-β. Both CD4+ and CD8+ T cells were involved in IFN-γ and IL-10 production. Interestingly, the retention and maintenance of residual IL-10 and TGF-β in some SAG-treated individuals and the elevation of IL-10 and TGF-β in PKDL, a sequel to kala-azar, probably reflects the role of these cytokines in reactivation of the disease in the form of PKDL. Contrastingly, AmB treatment of VL resulted in negligible TGF-β levels and absolute elimination of IL-10, reflecting the better therapeutic activity of AmB and its probable role in the recent decline in PKDL occurrences in India. Moreover, elucidation of immune responses in Indian PKDL patients revealed a spectral pattern of disease progression where disease severity could be correlated inversely with lymphoproliferation and directly with TGF-β, IL-10, and Ab production. In addition, the enhancement of CD4+CD25+ T cells in active VL, their decline at cure, and reactivation in PKDL suggest their probable immunosuppressive role in these disease forms.

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“…In murine models of leishmaniasis, it is widely assumed that resistance to the disease is correlated with the production of IFN-γ by Th 1 cells, while susceptibility is associated with Th 2 response, resulting in IL-4 production (Heinzel et al 1989, Gumy et al 2004, although in visceral leishmaniasis this clear-cut role of Th 1 /Th 2 is less evident (Honoré et al 1998).…”

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confidence: 99%

Studies in a co-infection murine model of Plasmodium chabaudi chabaudi and Leishmania infantum: interferon<FONT FACE=Symbol>-g</FONT> and interleukin-4 mRNA expression

Marques

Rolão

Centeno-Lima

et al. 2005

Mem. Inst. Oswaldo Cruz

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The murine model of infection with Leishmania major and its importance for the deciphering of mechanisms underlying differences in Th cell differentiation in mice from different genetic backgrounds

Cited by 77 publications

References 122 publications

Regulatory B Cells Shape the Development of Th2 Immune Responses in BALB/c Mice Infected with Leishmania major Through IL-10 Production

Regulatory B Cells Shape the Development of Th2 Immune Responses in BALB/c Mice Infected with Leishmania major Through IL-10 Production

IL-10- and TGF-β-Mediated Susceptibility in Kala-azar and Post-kala-azar Dermal Leishmaniasis: The Significance of Amphotericin B in the Control of Leishmania donovani Infection in India

Studies in a co-infection murine model of Plasmodium chabaudi chabaudi and Leishmania infantum: interferon<FONT FACE=Symbol>-g</FONT> and interleukin-4 mRNA expression

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