A comparative approach on the activation of the three complement system pathways in different hosts of Visceral Leishmaniasis after stimulation with Leishmania infantum

Tirado, Thais Cristina; Bavia, Lorena; Ambrosio, Altair Rogerio; Campos, Monique Paiva; Santiago, Marta de Almeida; Messias-Reason, Iara José de; Figueiredo, Fabiano Borges

doi:10.1016/j.dci.2021.104061

Cited by 7 publications

(3 citation statements)

References 28 publications

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“…It was previously shown that infection with L. amazonensis promastigotes caused a reduction in complement in mice. Complement-depleted mice showed a reduced inflammatory response and cell infiltrate and phagocytosis along with an increased parasite burden ( 46 ). A recent paper reported that L. infantum promastigotes activated both the classical and alternative pathways to different extents in different sera (dog, cat, and human) but each caused functional depletion of both pathways ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

C-reactive protein binds to short phosphoglycan repeats of Leishmania secreted proteophosphoglycans and activates complement

Seow,

Doran,

Schroeder

et al. 2023

Front. Immunol.

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Human C-reactive protein (CRP) binds to lipophosphoglycan (LPG), a virulence factor of Leishmania spp., through the repeating phosphodisaccharide region. We report here that both major components of promastigote secretory gel (PSG), the filamentous proteophosphoglycan (fPPG) and the secreted acid phosphatase (ScAP), are also ligands. CRP binding was mainly associated with the flagellar pocket when LPG deficient Leishmania mexicana parasites were examined by fluorescent microscopy, consistent with binding to secreted material. ScAP is a major ligand in purified fPPG from parasite culture as demonstrated by much reduced binding to a ScAP deficient mutant fPPG in plate binding assays and ligand blotting. Nevertheless, in sandfly derived PSG fPPG is a major component and the major CRP binding component. Previously we showed high avidity of CRP for LPG ligand required multiple disaccharide repeats. ScAP and fPPG only have short repeats but they retain high avidity for CRP revealed by surface plasmon resonance because they are found in multiple copies on the phosphoglycan. The fPPG from many species such as L. donovani and L. mexicana bound CRP strongly but L. tropica and L. amazonensis had low amounts of binding. The extent of side chain substitution of [-PO4-6Galβ1-4Manα1-] disaccharides correlates inversely with binding of CRP. The ligand for the CRP on different species all had similar binding avidity as the half maximal binding concentration was similar. Since the PSG is injected with the parasites into host blood pools and phosphoglycans (PG) are known to deplete complement, we showed that CRP makes a significant contribution to the activation of complement by PSG using serum from naive donors.

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Section: Discussionmentioning

confidence: 99%

C-reactive protein binds to short phosphoglycan repeats of Leishmania secreted proteophosphoglycans and activates complement

Seow,

Doran,

Schroeder

et al. 2023

Front. Immunol.

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“…In fact, while dogs with a chronic disease show a prevalence of Th2 response, there is not a clear Th1/Th2 dichotomy in the T-cell response in human leishmaniasis [ 24 ]. Moreover, a recent work evidenced the variability of immune response between humans and dogs related to differences in complement proteins amount [ 25 ], which could play an important role in parasite inactivation due to the different lytic properties, affecting the clinical manifestations [ 26 ]. Nevertheless, the differences in immune responses related to ER stress and miRNA dysregulation have not been investigated yet.…”

Section: Discussionmentioning

confidence: 99%

The host micro-RNA cfa-miR-346 is induced in canine leishmaniasis

et al. 2022

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Background Leishmaniases are a group of anthropo-zoonotic parasitic diseases caused by a protozoan of the Leishmania genus, affecting both humans and other vertebrates, including dogs. L. infantum is responsible for the visceral and occasionally cutaneous form of the disease in humans and canine leishmaniasis. Previously, we have shown that L. infantum induces a mild but significant increase in endoplasmic reticulum (ER) stress expression markers to promote parasites survival in human and murine infected macrophages. Moreover, we demonstrated that the miRNA hsa-miR-346, induced by the UPR-activated transcription factor sXBP1, was significantly upregulated in human macrophages infected with different L. infantum strains. However, the ER stress response in infected dogs, which represent an important reservoir for Leishmania parasite, was described once recently, whereas the miR-346 expression was not reported before. Therefore, this study aimed to investigate these pathways in the canine macrophage-like cell line DH82 infected by Leishmania spp. and to evaluate the presence of cfa-miR-346 in plasma of non-infected and infected dogs. The DH82 cells were infected with L. infantum and L. braziliensis parasites and the expression of cfa-mir-346 and several ER stress markers was evaluated by quantitative PCR (qPCR) at different time points. Furthermore, the cfa-miR-346 was monitored in plasma collected from non-infected dogs (n = 11) and dogs naturally infected by L. infantum (n = 18). Results The results in DH82 cells showed that cfa-mir-346 was induced at both 24 h and 48 h post-infection with all Leishmania strains but not with tunicamycin, accounting for a mechanism of induction independent from sXBP1, unlike what was previously observed in human cell lines. Moreover, the cfa-miR-346 expression analysis on plasma revealed a significant increase in infected dogs compared to non-infected dogs. Conclusions Here for the first time, we report the upregulation of cfa-miR-346 induced by Leishmania infection in canine macrophage-like cells and plasma samples of naturally infected dogs. According to our results, the cfa-miR-346 appears to be linked to infection, and understanding its role and identifying its target genes could contribute to elucidate the mechanisms underlying the host–pathogen interaction in leishmaniasis.

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“…This finding is important to highlight that Leishmania parasites can elicit a protective cell-mediated immune response in cats. The only study assessing the role of the complement system in feline L. infantum infection showed that, contrary to humans and dogs, catʼs proteins are consumed by parasites in the lectin pathway, which hypothetically may justify their low predisposition to develop clinical disease ( Tirado et al., 2021 ).…”

Section: Immunopathogenesismentioning

confidence: 99%

Leishmania infection in cats and feline leishmaniosis: An updated review with a proposal of a diagnosis algorithm and prevention guidelines

Pereira¹,

Maia²

2021

Current Research in Parasitology & Vector-Borne Diseases

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A comparative approach on the activation of the three complement system pathways in different hosts of Visceral Leishmaniasis after stimulation with Leishmania infantum

Cited by 7 publications

References 28 publications

C-reactive protein binds to short phosphoglycan repeats of Leishmania secreted proteophosphoglycans and activates complement

C-reactive protein binds to short phosphoglycan repeats of Leishmania secreted proteophosphoglycans and activates complement

The host micro-RNA cfa-miR-346 is induced in canine leishmaniasis

Leishmania infection in cats and feline leishmaniosis: An updated review with a proposal of a diagnosis algorithm and prevention guidelines

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