Leishmania mexicana promastigotes inhibit macrophage IL-12 production via TLR-4 dependent COX-2, iNOS and arginase-1 expression

Shweash, Muhannad; McGachy, H. Adrienne; Schroeder, Joanna L.; Neamatallah, Thikryat; Bryant, Clare E.; Millington, Owain R.; Mottram, Jeremy C.; Alexander, James; Plevin, Robin

doi:10.1016/j.molimm.2011.05.013

Cited by 52 publications

(46 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As previously shown for macrophages infected with Leishmania mexicana (50), we also found that DC infection by L. amazonensis increases the phosphorylation of these three kinases. However, the increase of phosphorylation of JNK and p38 in infected cells was independent of A 2B receptor.…”

Section: Discussionsupporting

confidence: 90%

Leishmania amazonensis-Induced cAMP Triggered by Adenosine A2B Receptor Is Important to Inhibit Dendritic Cell Activation and Evade Immune Response in Infected Mice

et al. 2017

View full text Add to dashboard Cite

Differently from others Leishmania species, infection by the protozoan parasite L. amazonensis is associated with a lack of antigen-specific T-cell responses. Dendritic cells (DC) are essential for the innate immune response and for directing the differentiation of T-helper lymphocytes. Previously, we showed that L. amazonensis infection impairs DC activation through the activation of adenosine A2B receptor, and here, we evaluated the intracellular events triggered by this receptor in infected cells. To this aim, bone marrow-derived DC from C57BL/6J mice were infected with metacyclic promastigotes of L. amazonensis. Our results show, for the first time, that L. amazonensis increases the production of cAMP and the phosphorylation of extracellular signal-regulated protein kinases 1/2 (ERK1/2) in infected DC by a mechanism dependent on the A2B receptor. Furthermore, L. amazonensis impairs CD40 expression and IL-12 production by DC, and the inhibition of adenylate cyclase, phosphoinositide 3-kinase (PI3K), and ERK1/2 prevent these effects. The increase of ERK1/2 phosphorylation and the inhibition of DC activation by L. amazonensis are independent of protein kinase A (PKA). In addition, C57BL/6J mice were inoculated in the ears with metacyclic promastigotes, in the presence of PSB1115, an A2B receptor antagonist. PSB1115 treatment increases the percentage of CD40+ DC on ears and draining lymph nodes. Furthermore, this treatment reduces lesion size and tissue parasitism. Lymph node cells from treated mice produce higher levels of IFN-γ than control mice, without altering the production of IL-10. In conclusion, we suggest a new pathway used by the parasite (A2B receptor → cAMP → PI3K → ERK1/2) to suppress DC activation, which may contribute to the decrease of IFN-γ production following by the deficiency in immune response characteristic of L. amazonensis infection.

show abstract

Section: Discussionsupporting

confidence: 90%

Leishmania amazonensis-Induced cAMP Triggered by Adenosine A2B Receptor Is Important to Inhibit Dendritic Cell Activation and Evade Immune Response in Infected Mice

et al. 2017

View full text Add to dashboard Cite

show abstract

“…COX-2 is the inducible isoform of COX pro-inflammatory enzyme [53] associated with the production of proteinoids under inflammatory conditions [64], such that it is expressed in only a few normal tissues and upregulated in inflamed tissues. A previous study showed that L. mexicana prolonged the induction of COX-2 in macrophages stimulated with LPS [59]. Thus, its expression was expected, although no differences were observed between lesions from Balb/c and C57BL/6 mice.…”

Section: Discussionmentioning

confidence: 79%

Immunohistochemical evidence of stress and inflammatory markers in mouse models of cutaneous leishmaniosis

Araújo

Giorgio

2015

Arch Dermatol Res

View full text Add to dashboard Cite

Leishmanioses are chronic parasitic diseases and host responses are associated with pro- or anti-inflammatory cytokines involved, respectively, in the control or exacerbation of infection. The relevance of other inflammatory mediators and stress markers has not been widely studied and there is a need to search for biomarkers to leishmaniasis. In this work, the stress and inflammatory molecules p38 mitogen-activated protein kinase, cyclooxygenase-2, migration inhibitory factor, macrophage inflammatory protein 2, heat shock protein 70 kDa, vascular endothelial factor (VEGF), hypoxia-inducible factors (HIF-1α and HIF-2α), heme oxygenase and galectin-3 expression were assessed immunohistochemically in self-controlled lesions in C57BL/6 mice and severe lesions in Balb/c mice infected with Leishmania amazonensis. The results indicated that the majority of molecules were expressed in the cutaneous lesions of both C57BL/6 and Balb/c mice during various phases of infection, suggesting no obvious correlation between the stress and inflammatory molecule expression and the control/exacerbation of leishmanial lesions. However, the cytokine VEGF was only detected in C57BL/6 footpad lesions and small lesions in Balb/c mice treated with antimonial pentavalent. These findings suggest that VEGF expression could be a predictive factor for murine leishmanial control, a hypothesis that should be tested in human leishmaniosis.

show abstract

“…Increasing evidence is indeed accumulating showing that the formation of ROS represents an essential pathway of TLR-dependent signaling in cells from immune and non-immune origin, which occurs mainly through the activation of various NOX isoforms (Tsung et al, 2007;Ogier-Denis et al, 2008;Gill et al, 2010). In addition, the pro-inflammatory signaling cascades triggered by TLR engagement enhance the expression of iNOS, and thus promotes the generation of NO (Lewis et al, 2011;Shweash et al, 2011). In turn, the concomitant generation of O 2 .-(by NOXs) and NO .…”

Section: Role Of Tlr Activation In the Generation Of Oxidantsmentioning

confidence: 99%

The role of oxidative stress during inflammatory processes

Lugrin¹,

Rosenblatt‐Velin

Parapanov³

et al. 2013

Biological Chemistry

580

393

View full text Add to dashboard Cite

Abstract:The production of various reactive oxidant species in excess of endogenous antioxidant defense mechanisms promotes the development of a state of oxidative stress, with significant biological consequences. In recent years, evidence has emerged that oxidative stress plays a crucial role in the development and perpetuation of inflammation, and thus contributes to the pathophysiology of a number of debilitating illnesses, such as cardiovascular diseases, diabetes, cancer, or neurodegenerative processes. Oxidants affect all stages of the inflammatory response, including the release by damaged tissues of molecules acting as endogenous danger signals, their sensing by innate immune receptors from the Toll-like (TLRs) and the NOD-like (NLRs) families, and the activation of signaling pathways initiating the adaptive cellular response to such signals. In this article, after summarizing the basic aspects of redox biology and inflammation, we review in detail the current knowledge on the fundamental connections between oxidative stress and inflammatory processes, with a special emphasis on the danger molecule highmobility group box-1, the TLRs, the NLRP-3 receptor, and the inflammasome, as well as the transcription factor nuclear factor-κB.

show abstract

Leishmania mexicana promastigotes inhibit macrophage IL-12 production via TLR-4 dependent COX-2, iNOS and arginase-1 expression

Cited by 52 publications

References 49 publications

Leishmania amazonensis-Induced cAMP Triggered by Adenosine A2B Receptor Is Important to Inhibit Dendritic Cell Activation and Evade Immune Response in Infected Mice

Leishmania amazonensis-Induced cAMP Triggered by Adenosine A2B Receptor Is Important to Inhibit Dendritic Cell Activation and Evade Immune Response in Infected Mice

Immunohistochemical evidence of stress and inflammatory markers in mouse models of cutaneous leishmaniosis

The role of oxidative stress during inflammatory processes

Contact Info

Product

Resources

About