Leishmania major and Toxoplasma gondii have opposite effects on cytokine synthesis by macrophages

Carrera, Lucia; Chiaramonte, Mónica G.; Kühn, Rolf; Müller, Werner; Sacks, David L.; Sher, Alan; Gazzinelli, Ricardo T.

doi:10.1590/s0074-02761994000400024

Cited by 4 publications

(4 citation statements)

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“…IL-12 is produced following in vivo infection of mice by Leishmania (27,28), and is important to control Th2 expansion and promote the predominance of a Th1 type of response (28)(29)(30). In vitro, however, the parasite is able to inhibit IL-12 production by the infected macrophages (31,32). Treatment of susceptible animals with IL-12 renders them resistant (30,(33)(34)(35), and has also been used as an effective adjuvant for a killed vaccine for L. major (36).…”

Section: Il-12 and Host Protectionmentioning

confidence: 99%

Human_Leishmaniasis@cytokines.bahia.br

Barral‐Netto

Brodskyn

Carvalho

et al. 1998

Braz J Med Biol Res

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Section: Il-12 and Host Protectionmentioning

confidence: 99%

Human_Leishmaniasis@cytokines.bahia.br

Barral‐Netto

Brodskyn

Carvalho

et al. 1998

Braz J Med Biol Res

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“…Interestingly, in vitro infection of macrophages with either L. major or L. donovani does not result in induction of IL-12 synthesis by macrophages, even when the cells are primed with IFN-γ (18,19,31) (Figure 1). In fact, infection with Leishmania leads to complete and selective inhibition of IL-12 synthesis by macrophage host cells activated with different microbial stimuli (19), but has no significant inhibitory effect on the expression of other inducible genes such as IL-1α, IL-1ß, TNF-α, inducible nitric oxide synthase (iNOS) or IL-10.…”

Section: Impairment Of Il-12 Synthesis By Macrophages Infected In Vitmentioning

confidence: 99%

“…In fact, infection with Leishmania leads to complete and selective inhibition of IL-12 synthesis by macrophage host cells activated with different microbial stimuli (19), but has no significant inhibitory effect on the expression of other inducible genes such as IL-1α, IL-1ß, TNF-α, inducible nitric oxide synthase (iNOS) or IL-10. A possible mechanism for selective inhibition of IL-12 synthesis by macrophages would involve binding to complement receptors, since triggering of complement receptors has been shown to selectively induce IL-12 synthesis by macrophages (32,33).…”

Section: Impairment Of Il-12 Synthesis By Macrophages Infected In Vitmentioning

confidence: 99%

“…Several studies indicate that Leishmania may use different strategies to evade induction of macrophage effector functions (16,17). Probably the most powerful strategy is to inhibit the synthesis of IFN-γ, a cytokine which leads to the activation of macrophage effector functions (18,19). A second strategy would be the inhibition of effector functions in macrophages exposed to IFN-γ (20).…”

Section: Introductionmentioning

confidence: 99%

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Induction of cell-mediated immunity during early stages of infection with intracellular protozoa

Gazzinelli

Talvani

Camargo

et al. 1998

Braz J Med Biol Res

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Toxoplasma gondii and Trypanosoma cruzi are intracellular parasites which, as part of their life cycle, induce a potent cell-mediated immunity (CMI) maintained by Th1 lymphocytes and IFN-γ. In both cases, induction of a strong CMI is thought to protect the host against rapid parasite multiplication and consequent pathology and lethality during the acute phase of infection. However, the parasitic infection is not eliminated by the immune system and the vertebrate host serves as a parasite reservoir. In contrast, Leishmania sp, which is a slow growing parasite, appears to evade induction of CMI during early stages of infection as a strategy for surviving in a hostile environment (i.e., inside the macrophages which are their obligatory niche in the vertebrate host). Recent reports show that the initiation of IL-12 synthesis by macrophages during these parasitic infections is a key event in regulating CMI and disease outcome. The studies reviewed here indicate that activation/inhibition of distinct signaling pathways and certain macrophage functions by intracellular protozoa are important events in inducing/modulating the immune response of their vertebrate hosts, allowing parasite and host survival and therefore maintaining parasite life cycles.

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Toxoplasma gondii antigen SAG2A differentially modulates IL-1β expression in resistant and susceptible murine peritoneal cells

Leal-Sena

Santos

et al. 2018

Appl Microbiol Biotechnol

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The cell surface of Toxoplasma gondii is covered by antigens (SAGs) from the SRS family anchored by glycosylphosphatidylinositol (GPI) and includes antigens from the SAG2 family. Among these, the SAG2A surface antigen shows great potential in activating humoral responses and has been used in characterizing the acute phase of infection and in the serological diagnosis of toxoplasmosis. In this study, we aimed to evaluate rSAG2A-induced proteins in BALB/c and C57BL/c mice macrophages and to evaluate the phenotypic polarization induced in the process. We treated the peritoneal macrophages from mouse strains that were resistant or susceptible to T. gondii with rSAG2A to analyze their proteomic profile by mass spectrometry and systems biology. We also examined the gene expression of these cells by RT-qPCR using the phenotypic markers of M1 and M2 macrophages. Differences were observed in the expression of proteins involved in the inflammatory process in both resistant and susceptible cells, and macrophages were preferentially induced to obtain a pro-inflammatory immune response (M1) via the overexpression of IL-1β in mice susceptible to this parasite. These data suggest that the SAG2A antigen induces phenotypic and classical activation of macrophages in both resistant and susceptible strains of mice during the acute phase of the disease.

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Leishmania major and Toxoplasma gondii have opposite effects on cytokine synthesis by macrophages

Cited by 4 publications

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Human_Leishmaniasis@cytokines.bahia.br

Human_Leishmaniasis@cytokines.bahia.br

Induction of cell-mediated immunity during early stages of infection with intracellular protozoa

Toxoplasma gondii antigen SAG2A differentially modulates IL-1β expression in resistant and susceptible murine peritoneal cells

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