Leishmania major: Recruitment of Gr-1+ cells into draining lymph nodes during infection is important for early IL-12 and IFNγ production

Santos, Milla Schmaltz Tatico dos; Cardoso, Ludimila Paula Vaz; Nascimento, Gustavo Rios; Junior, Ruy de Sousa Lino; Dorta, Miriam Leandro; Oliveira, Milton Adriano Pelli de; Ribeiro‐Dias, Fátima

doi:10.1016/j.exppara.2008.04.011

Cited by 10 publications

(9 citation statements)

References 38 publications

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“…During chronic Leishmania major infection, myeloid precursors circulate in the blood, and purified blood monocytes phagocytose L. major promastigotes [7]. In addition, Gr1 hi cells are recruited to draining LNs [13]. Furthermore, immature mononuclear cells infiltrate skin lesions in acute infection by L. major [14 -16], where they may act as host and effector cells [17].…”

Section: Introductionmentioning

confidence: 99%

Myeloid-derived suppressor cells help protective immunity toLeishmania majorinfection despite suppressed T cell responses

Pereira

Ribeiro-Gomes

Guillermo

et al. 2011

Journal of Leukocyte Biology

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Th1/Th2 cytokines play a key role in immune responses to Leishmania major by controlling macrophage activation for NO production and parasite killing. MDSCs, including myeloid precursors and immature monocytes, produce NO and suppress T cell responses in tumor immunity. We hypothesized that NO-producing MDSCs could help immunity to L. major infection. Gr1(hi)(Ly6C(hi)) CD11b(hi) MDSCs elicited by L. major infection suppressed polyclonal and antigen-specific T cell proliferation. Moreover, L. major-induced MDSCs killed intracellular parasites in a NO-dependent manner and reduced parasite burden in vivo. By contrast, treatment with ATRA, which induces MDSCs to differentiate into macrophages, increased development of lesions, parasite load, and T cell proliferation in draining LNs. Altogether, these results indicate that NO-producing MDSCs help protective immunity to L. major infection, despite suppressed T cell proliferation.

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Section: Introductionmentioning

confidence: 99%

Myeloid-derived suppressor cells help protective immunity toLeishmania majorinfection despite suppressed T cell responses

Pereira

Ribeiro-Gomes

Guillermo

et al. 2011

Journal of Leukocyte Biology

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“…Granulocytes (Gr-1 high CD11c Ϫ PDCA-1 Ϫ (25-27)) were also induced to migrate following LPS-DC injections in animals pretreated with BALB/c splenocytes. Granulocytes have a major role in innate immunity, but recent evidence indicates that they also contribute to adaptive immunity (28). They attract immature DC via the release of MIP-1␣, MIP-1␤, and ␣-defensins, they interact with DC (29), they induce DC maturation partially through the release of TNF-␣, and they instruct DC to induce Th1 polarization (30).…”

Section: Activated Regulatory T Cells Inhibit Early Activation and Acmentioning

confidence: 99%

“…4B). To best reflect the in vivo situation, homogenized draining LN were cultured for 48 h, and supernatants were harvested (28). The profile of proinflammatory cytokines mirrored the proliferation and activation data in the draining LN.…”

Section: Superantigen-dependent Suppression Of Ova-specific Naive T Cmentioning

confidence: 99%

Superantigen-Activated Regulatory T Cells Inhibit the Migration of Innate Immune Cells and the Differentiation of Naive T Cells

Tanriver

Martín-Fontecha²,

Ratnasothy³

et al. 2009

The Journal of Immunology

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Regulatory T cells can be used as tools to suppress pathogenic T cells in autoimmunity, graft-vs-host-disease, and transplantation. But even when high numbers of Ag-specific regulatory T cells are available, it is still possible under certain in vivo and in vitro conditions for effector T cells to escape effective control. Current reports suggest that the degree of suppression is modulated by the inflammatory milieu, which can induce resistance to suppression in effector T cells or subvert the inhibitory function of the regulatory T cells. Cells of the innate immune system integrate early signals of injury and infection and have a major impact on the ensuing inflammation. Hence, the modification of these initial events can be key to allowing suppression to dominate. The approach we took here was to test whether the in vivo preactivation of endogenous regulatory T cells with a superantigen could enhance their suppressive potency. We provide evidence that this not only proved effective in expanding the pool of preactivated regulatory T cells but also in preventing the migration of NK cells and granulocytes upon sensitization with matured dendritic cells. The attenuation of innate immune activation was accompanied by linked suppression of adoptively transferred OVA-specific T cells when APC coexpressing OVA and the superantigen were injected. These data suggest that the preactivation of regulatory T cells is a promising approach to increase their potency.

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“…The intrinsic susceptibility of the Ethiopian population suffering from leishmaniasis through the generation of myeloid cells indicates the significance of myeloid cells (among which MDSCs are included) from a therapeutic point of view (13). Despite suppressed T cell functions, Gr1 ϩ cells have been shown to be essential for the production of early Th1 cytokines in murine draining lymph nodes (14). However, the suppression mechanism of MDSCs includes production of cyclooxygenase-2 (Cox-2) and arginase I and blocking of T cell function by depleting L-arginine (15).…”

mentioning

confidence: 99%

Glycyrrhizic Acid-Mediated Subdual of Myeloid-Derived Suppressor Cells Induces Antileishmanial Immune Responses in a Susceptible Host

et al. 2015

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CD11b؉ Gr1 ؉ myeloid-derived suppressor cells (MDSCs), a heterogeneous population of precursor cells, modulate protective immunity against visceral leishmaniasis by suppressing T cell functions. We observed that CD11b ϩ cells have been shown to be essential for the production of early Th1 cytokines in murine draining lymph nodes (14). However, the suppression mechanism of MDSCs includes production of cyclooxygenase-2 (Cox-2) and arginase I and blocking of T cell function by depleting L-arginine (15). Interestingly, pharmacological inhibition of Cox-2 blocked the expression of arginase I in lung carcinoma (16), though it was not clear how suppression of Cox-2 in MDSCs could affect Leishmania infection in a susceptible host.On the other hand, glycyrrhizic acid (GA), a predominant bioactive component of the root of Glycyrrhiza glabra, has been reported to evoke antileishmanial activity through regulation of Cox-2 production (17). MDSCs exert a suppressive function on T cells that is dependent on the production of arginase I (11, 12). We aimed to investigate how MDSCs and their pharmacological manipulation affect the host immune response against L. donovani infection. Here we show that MDSCs from soluble leishmanial antigen (SLA)-immunized BALB/c mice are less immunosuppressive than infection-induced MDSCs and fail to inhibit the induction of Th1 cytokines. Immunization of BALB/c mice with SLA resulted in reduced production of arginase I, Cox-2, inducible nitric oxide synthase (iNOS), and prostaglandin E2 (PGE2) in MDSCs. Moreover, pharmacological inhibition of Cox-2 by GA in BALB/c mice rendered the MDSCs nonsuppressive. In summary, we demonstrated an antileishmanial effect of Cox-2 inhibition by GA in myeloid-derived suppressor cells, a strategy that may be useful for eliminating the suppressive effect of MDSCs in relevant pathological contexts.

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Leishmania major: Recruitment of Gr-1+ cells into draining lymph nodes during infection is important for early IL-12 and IFNγ production

Cited by 10 publications

References 38 publications

Myeloid-derived suppressor cells help protective immunity toLeishmania majorinfection despite suppressed T cell responses

Myeloid-derived suppressor cells help protective immunity toLeishmania majorinfection despite suppressed T cell responses

Superantigen-Activated Regulatory T Cells Inhibit the Migration of Innate Immune Cells and the Differentiation of Naive T Cells

Glycyrrhizic Acid-Mediated Subdual of Myeloid-Derived Suppressor Cells Induces Antileishmanial Immune Responses in a Susceptible Host

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