<i>Leishmania donovani</i> development in <i>Phlebotomus argentipes</i>: comparison of promastigote- and amastigote-initiated infections

Sádlová, Jovana; Myšková, Jitka; Leštinová, Tereza; Votýpka, Jan; Yeo, Matthew; Volf, Petr

doi:10.1017/s0031182016002067

Cited by 24 publications

(23 citation statements)

References 38 publications

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“…Leishmania species are digenetic obligatory intracellular parasitic protozoans that reside inside two hostile environments i.e., the midgut of the insect vector, and the phagolysosomes of the mammalian macrophages (Sadlova et al, 2016 ). The initial interaction between the host cell and parasite determines whether parasite will make silent entry in macrophages and persist or host will eliminate the parasite (Stager et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of miRNAs in Response to Leishmania donovani Infection: Delineation of Their Roles in Macrophage Dysfunction

et al. 2017

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The outcome of Leishmania infection depends on parasite abilities to evade host immune response and its survival in hostile environment of host macrophages. Despite a wealth of gained crucial information, parasite strategies by which it dampens host macrophage functions remain poorly understood. Micro RNAs (miRNAs) are evolutionarily conserved class of endogenous 22-nucleotide small non-coding RNA gene products, described to participate in the regulation of almost every cellular process investigated so far. In this study, we identified 940 miRNAs in Leishmania donovani infected macrophages by de novo sequencing out of which levels of 85 miRNAs were found to be consistently modified by parasite infection. Herein, we report the functional characteristics of 10 miRNAs i.e., mir-3620, mir-6385, mir-6973a, mir-6996, mir-328, mir-8113, mir-3473f, mir-763, mir-6540, and mir-1264 that were differentially but constantly regulated in infected macrophages for their role in regulation of macrophage effector functions. The target gene prediction and biological interaction analysis revealed involvement of these miRNAs in various biological processes such as apoptosis inhibition, phagocytosis, drug response, and T cell phenotypic transitions. These findings could contribute for the better understanding of macrophages dysfunction and leishmanial pathogenesis. Further, the identified miRNAs could also be used as biomarker/s in diagnosis, prognosis, and therapeutics of Leishmania infection.

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Section: Discussionmentioning

confidence: 99%

Identification and Characterization of miRNAs in Response to Leishmania donovani Infection: Delineation of Their Roles in Macrophage Dysfunction

et al. 2017

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“…Body length, flagellar length and body width of parasites were measured using Image-J software. Four morphological forms were distinguished, as described in Sadlova et al [ 24 ]: procyclic promastigotes (PP), elongated nectomonads (EN), metacyclic promastigotes (MP) and short promastigotes (SP). Haptomonads were not distinguished as representation of these attached forms is in principle underestimated on gut smears.…”

Section: Methodsmentioning

confidence: 99%

Leishmania mortality in sand fly blood meal is not species-specific and does not result from direct effect of proteinases

et al. 2018

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BackgroundLeishmania development in sand flies is confined to the alimentary tract and is closely connected with blood meal digestion. Previously, it has been published that activities of sand fly midgut proteases are harmful to Leishmania, especially to amastigote-promastigote transition forms. However, our experiments with various Leishmania-sand fly pairs gave quite opposite results.MethodsWe evaluated the effect of semi-digested midgut content on different life stages of Leishmania donovani and Leishmania major in vitro. Various morphological forms of parasites, including macrophage-derived amastigotes and transition forms, were incubated 2 h with midguts dissected at various intervals (6–72 h) post-blood meal or with commercially available proteinase, and their viability was determined using flow cytometry. In parallel, using amastigote-initiated experimental infections, we compared development of L. donovani in sand flies that are either susceptible (Phlebotomus argentipes and P. orientalis) or refractory (P. papatasi and Sergentomyia schwetzi) to this parasite.ResultsIn vitro, sand fly midgut homogenates affected L. major and L. donovani in a similar way; in all sand fly species, the most significant mortality effect was observed by the end of the blood meal digestion process. Surprisingly, the most susceptible Leishmania stages were promastigotes, while mortality of transforming parasites and amastigotes was significantly lower. Parasites were also susceptible to killing by rabbit blood in combination with proteinase, but resistant to proteinase itself. In vivo, L. donovani developed late-stage infections in both natural vectors; in P. argentipes the development was much faster than in P. orientalis. On the other hand, in refractory species P. papatasi and S. schwetzi, promastigotes survived activity of digestive enzymes but were lost during defecation.ConclusionsWe demonstrated that Leishmania transition forms are more resistant to the killing effect of semi-digested blood meal than 24 h-old promastigotes. Data suggest that Leishmania mortality is not caused directly by sand fly proteases, we assume that this mortality results from toxic products of blood meal digestion. Survival of L. donovani promastigotes in refractory sand flies until blood meal defecation, together with similar mortality of Leishmania parasites incubated in vitro with midgut homogenates of susceptible as well as refractory species, contradict the previously raised hypotheses about the role of midgut proteases in sand fly vector competence to Leishmania.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-2613-2) contains supplementary material, which is available to authorized users.

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“…Early-stage infections were associated with substantial differences in both the parasitic load and the representation of morphological forms, and these differences gradually disappeared with increasing maturation of the infectious agent. This finding shows that use of the promastigote stage for sandfly infection does not significantly alter the final outcome of Leishmania donovani development in P. argentipes or the resulting transmissibility [62].…”

Section: Plos Pathogensmentioning

confidence: 76%

TLR4 abrogates the Th1 immune response through IRF1 and IFN-β to prevent immunopathology during L. infantum infection

et al. 2020

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A striking feature of human visceral leishmaniasis (VL) is chronic inflammation in the spleen and liver, and VL patients present increased production levels of multiple inflammatory mediators, which contribute to tissue damage and disease severity. Here, we combined an experimental model with the transcriptional profile of human VL to demonstrate that the TLR4-IFN-β pathway regulates the chronic inflammatory process and is associated with the asymptomatic form of the disease. Tlr4-deficient mice harbored fewer parasites in their spleen and liver than wild-type mice. TLR4 deficiency enhanced the Th1 immune response against the parasite, which was correlated with an increased activation of dendritic cells (DCs). Gene expression analyses demonstrated that IRF1 and IFN-β were expressed downstream of TLR4 after infection. Accordingly, IRF1-and IFNAR-deficient mice harbored fewer parasites in the target organs than wild-type mice due to having an increased Th1 immune response. However, the absence of TLR4 or IFNAR increased the serum transaminase levels in infected mice, indicating the presence of liver damage in these animals. In addition, IFN-β limits IFN-γ production by acting directly on Th1 cells. Using RNA sequencing analysis of human samples, we demonstrated that the transcriptional signature for the TLR4 and type I IFN (IFN-I) pathways was positively modulated in asymptomatic subjects compared with VL patients and thus provide direct evidence demonstrating that the TLR4-IFN-I pathway is related to the nondevelopment of the disease. In conclusion, our results demonstrate that the TLR4-IRF1 pathway culminates in IFN-β production as a mechanism

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Leishmania donovani development in Phlebotomus argentipes: comparison of promastigote- and amastigote-initiated infections

Cited by 24 publications

References 38 publications

Identification and Characterization of miRNAs in Response to Leishmania donovani Infection: Delineation of Their Roles in Macrophage Dysfunction

Identification and Characterization of miRNAs in Response to Leishmania donovani Infection: Delineation of Their Roles in Macrophage Dysfunction

Leishmania mortality in sand fly blood meal is not species-specific and does not result from direct effect of proteinases

TLR4 abrogates the Th1 immune response through IRF1 and IFN-β to prevent immunopathology during L. infantum infection

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