Resolvin D1 drives establishment of Leishmania amazonensis infection

Malta‐Santos, Hayna; Andrade, Bruno B.; Zanette, Dalila Lucíola; Costa, Jackson Maurício Lopes; Bozza, Patrı́cia T.; Bandeira‐Melo, Christianne; Barral, Aldina; França‐Costa, Jaqueline; Borges, Valéria M.

doi:10.1038/srep46363

Cited by 16 publications

(14 citation statements)

References 31 publications

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“…Previous studies from our group have shown that HO-1 favors Leishmania infection ( 20 , 21 ). Based on our findings, we have proposed that HO-1 plays two major roles following Leishmania infection: ( 1 ) it prevents host cell damage, and ( 2 ) it decreases the ability of the host to limit intracellular growth of the parasite.…”

Section: Introductionmentioning

confidence: 73%

Lutzomyia longipalpis Saliva Induces Heme Oxygenase-1 Expression at Bite Sites

et al. 2018

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Sand flies bite mammalian hosts to obtain a blood meal, driving changes in the host inflammatory response that support the establishment of Leishmania infection. This effect is partially attributed to components of sand fly saliva, which are able to recruit and activate leukocytes. Our group has shown that heme oxygenase-1 (HO-1) favors Leishmania survival in infected cells by reducing inflammatory responses. Here, we show that exposure to sand fly bites is associated with induction of HO-1 in vivo. Histopathological analyses of skin specimens from human volunteers experimentally exposed to sand fly bites revealed that HO-1 and Nrf2 are produced at bite sites in the skin. These results were recapitulated in mice ears injected with a salivary gland sonicate (SGS) or exposed to sand fly bites, indicating that vector saliva may be a key factor in triggering HO-1 expression. Resident skin macrophages were the main source HO-1 at 24–48 h after bites. Additionally, assays in vivo after bites and in vitro after stimulation with saliva both demonstrated that HO-1 production by macrophages was Nrf2-dependent. Collectively, our data demonstrates that vector saliva induces early HO-1 production at the bite sites, representing a major event associated with establishment of naturally-transmitted Leishmania infections.

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Section: Introductionmentioning

confidence: 73%

Lutzomyia longipalpis Saliva Induces Heme Oxygenase-1 Expression at Bite Sites

et al. 2018

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“…Regarding the role of these pro-resolving lipids in CL, RvD1 increases in patients with diffuse CL (DCL), in comparison with those with LCL, who had lower levels of RvD1 and higher levels of RvD2. This RvD1 pattern in DCL patients correlates with higher levels of Arginase-I and TGF-β and lower levels of TNF-α ( Malta-Santos et al, 2017 ). In an in vitro model of Leishmania infection based on human cells, RvD1 increased phagocytosis of the Leishmania parasites by human macrophages.…”

Section: Leishmania Spp Infectionsmentioning

confidence: 99%

“…In an in vitro model of Leishmania infection based on human cells, RvD1 increased phagocytosis of the Leishmania parasites by human macrophages. The increase of RvD1 in L. amazonensis -infected macrophages is reversed by baicalein, an inhibitor of 15-LO ( Malta-Santos et al, 2017 ).…”

Section: Leishmania Spp Infectionsmentioning

confidence: 99%

Inflammatory and Pro-resolving Lipids in Trypanosomatid Infections: A Key to Understanding Parasite Control

et al. 2018

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Pathogenic trypanosomatids (Trypanosoma cruzi, Trypanosoma brucei, and Leishmania spp.) are protozoan parasites that cause neglected diseases affecting millions of people in Africa, Asia, and the Americas. In the process of infection, trypanosomatids evade and survive the immune system attack, which can lead to a chronic inflammatory state that induces cumulative damage, often killing the host in the long term. The immune mediators involved in this process are not entirely understood. Most of the research on the immunologic control of protozoan infections has been focused on acute inflammation. Nevertheless, when this process is not terminated adequately, permanent damage to the inflamed tissue may ensue. Recently, a second process, called resolution of inflammation, has been proposed to be a pivotal process in the control of parasite burden and establishment of chronic infection. Resolution of inflammation is an active process that promotes the normal function of injured or infected tissues. Several mediators are involved in this process, including eicosanoid-derived lipids, cytokines such as transforming growth factor (TGF)-β and interleukin (IL)-10, and other proteins such as Annexin-V. For example, during T. cruzi infection, pro-resolving lipids such as 15-epi-lipoxin-A4 and Resolvin D1 have been associated with a decrease in the inflammatory changes observed in experimental chronic heart disease, reducing inflammation and fibrosis, and increasing host survival. Furthermore, Resolvin D1 modulates the immune response in cells of patients with Chagas disease. In Leishmania spp. infections, pro-resolving mediators such as Annexin-V, lipoxins, and Resolvin D1 are related to the modulation of cutaneous manifestation of the disease. However, these mediators seem to have different roles in visceral or cutaneous leishmaniasis. Finally, although T. brucei infections are less well studied in terms of their relationship with inflammation, it has been found that arachidonic acid-derived lipids act as key regulators of the host immune response and parasite burden. Also, cytokines such as IL-10 and TGF-β may be related to increased infection. Knowledge about the inflammation resolution process is necessary to understand the host–parasite interplay, but it also offers an interesting opportunity to improve the current therapies, aiming to reduce the detrimental state induced by chronic protozoan infections.

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“…Previous in vitro studies have demonstrated the role of LTB 4 as a parasite killing mechanism, while PGE 2 favors Leishmania survival 23 – 28 . More recently, lipid mediators have been identified as biomarkers during cutaneous 29 , 30 and visceral leishmaniasis 31 . In addition, L .…”

Section: Introductionmentioning

confidence: 99%

Leishmania infantum lipophosphoglycan induced-Prostaglandin E2 production in association with PPAR-γ expression via activation of Toll like receptors-1 and 2

Lima

Araújo-Santos

Lázaro-Souza

et al. 2017

Sci Rep

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Lipophosphoglycan (LPG) is a key virulence factor expressed on the surfaces of Leishmania promastigotes. Although LPG is known to activate macrophages, the underlying mechanisms resulting in the production of prostaglandin E2 (PGE2) via signaling pathways remain unknown. Here, the inflammatory response arising from stimulation by Leishmania infantum LPG and/or its lipid and glycan motifs was evaluated with regard to PGE2 induction. Intact LPG, but not its glycan and lipid moieties, induced a range of proinflammatory responses, including PGE2 and nitric oxide (NO) release, increased lipid droplet formation, and iNOS and COX2 expression. LPG also induced ERK-1/2 and JNK phosphorylation in macrophages, in addition to the release of PGE2, MCP-1, IL-6, TNF-α and IL-12p70, but not IL-10. Pharmacological inhibition of ERK1/2 and PKC affected PGE2 and cytokine production. Moreover, treatment with rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ), also modulated the release of PGE2 and other proinflammatory mediators. Finally, we determined that LPG-induced PPAR-γ signaling occurred via TLR1/2. Taken together, these results reinforce the role played by L. infantum-derived LPG in the proinflammatory response seen in Leishmania infection.

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Resolvin D1 drives establishment of Leishmania amazonensis infection

Cited by 16 publications

References 31 publications

Lutzomyia longipalpis Saliva Induces Heme Oxygenase-1 Expression at Bite Sites

Lutzomyia longipalpis Saliva Induces Heme Oxygenase-1 Expression at Bite Sites

Inflammatory and Pro-resolving Lipids in Trypanosomatid Infections: A Key to Understanding Parasite Control

Leishmania infantum lipophosphoglycan induced-Prostaglandin E2 production in association with PPAR-γ expression via activation of Toll like receptors-1 and 2

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