Modulation of Host Immune Response during Leishmania infantum Natural Infection: A Whole-Transcriptome Analysis of the Popliteal Lymph Nodes in Dogs

Sanz, C. R.; Miró, Guadalupe; Sevane, Natalia; Reyes-Palomares, Armando; Dunner, S.

doi:10.3389/fimmu.2021.794627

Cited by 11 publications

(8 citation statements)

References 157 publications

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“…A significant induction of ER stress expression markers -including sXBP1 was observed after 48 h post-infection. Similar results have been obtained from the transcriptome analysis in dogs naturally infected where an overexpression of XBP1 and some other genes involved in ER stress and UPR have been evidenced in lymph nodes [ 27 ]. On the other hand, the cfa-mir-346 was always significantly upregulated after infection with all Leishmania strains and at all times tested, including 24 h from infection, when the expression of ER stress markers was still unchanged.…”

Section: Discussionsupporting

confidence: 83%

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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Section: Discussionsupporting

confidence: 83%

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

et al. 2022

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“…A decrease in IL-8 levels has been reported in dogs infected both naturally and experimentally [43]. However, contrarily, it has been stated that amastigotes accumulate and survive in neutrophils in animals with high IL-8 levels [44], although these results are not conclusive. In humans, IL-8 polymorphism has been considered a risk factor for the development of visceral leishmaniasis [45].…”

Section: Discussionmentioning

confidence: 93%

Immunological and genomic characterization of Ibizan Hound dogs in an endemic Leishmania infantum region

2022

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Background The Ibizan Hound is a canine breed native to the Mediterranean region, where leishmaniosis is an endemic zoonosis. Several studies indicate low prevalence of this disease in these dogs but the underlying molecular mechanism remains unknown. Methods In this study, qualitative immunological and genomic profiles of this breed have been analyzed. Results Our analysis shows relevant differences between the cytokine serum profile of Ibizan Hound dogs and previously published data from other canine strains. Additionally, several genetic risk variants related to the immune response, regulation of the immune system, and genes encoding cytokines and their receptors have been studied. The most relevant genes that presented such fixed polymorphisms were IFNG and IL6R. Other variants with frequencies ≥ 0.7 were found in the genes ARHGAP18, DAPK1, GNAI2, MITF, IL12RB1, LTBP1, SCL28A3, SCL35D2, PTPN22, CIITA, THEMIS, and CD180. Epigenetic regulatory genes such as HEY2 and L3MBTL3 showed also intronic polymorphisms. Conclusions Our analysis and results indicate that the regulation of immune responses is different in Ibizan Hounds compared to other breeds. Future studies are needed to elucidate whether these differences are related to the low prevalence of L. infantum infection in the Ibizan Hound. Graphical Abstract

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“…A decrease in its levels has been noted in dogs infected, both naturally and experimentally [50]. In disagree with this, it has been stated that amastigotes accumulate and survive in neutrophils in animals with high IL-8 levels [51], although the studies developed are not conclusive. In humans, IL-8 polymorphism has been considered a risk factor for the development of visceral leishmaniasis [52].…”

Section: Discussionmentioning

confidence: 97%

Immune and genomic characterization of Ibizan hound and its relationship with Leishmania infantum infection

Álvarez

Marín-García

Llobat

2022

Preprint

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Ibizan hound is a canine breed native to the Mediterranean region, where leishmaniosis is an endemic zoonosis. Several studies indicate low prevalence of this disease in these dogs. In this study, descriptive immunological and genomic profiles of this breed have been elaborated. Results show relevant differences between the cytokine serum profile and the data published for other canine breeds, and several genetic fixed variants in genes related to immune response, regulation of immune system, and genes encode cytokines and its receptors in dog population studied. The most relevant genes that present such fixed polymorphisms were IFNG and IL6R. Other variants with frequencies equal or above 0.7 were found in the genes ARHGAP18, DAPK1, GNAI2, MITF, IL12RB1, LTBP1, SCL28A3, SCL35D2, PTPN22, CIITA, THEMIS, CD180. Epigenetic regulatory genes as HEY2, L3MBTL3 show also intronic polymorphisms. Results pointed out that the regulation of immune response is different in the Ibizan hound dogs compared to other breeds. Future studies are needed to elucidate detected differences and their relationship to low prevalence of L. infantum infection in the breed.

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Modulation of Host Immune Response during Leishmania infantum Natural Infection: A Whole-Transcriptome Analysis of the Popliteal Lymph Nodes in Dogs

Cited by 11 publications

References 157 publications

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

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

Immunological and genomic characterization of Ibizan Hound dogs in an endemic Leishmania infantum region

Immune and genomic characterization of Ibizan hound and its relationship with Leishmania infantum infection

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