Leishmania infantum Induces the Release of sTREM-1 in Visceral Leishmaniasis

Bomfim, Lays Gisele Santos; Magalhães, Lucas Sousa; Santos-Filho, Marcello A. A.; Peres, Nalu T. A.; Corrêa, Cristiane Bani; Tanajura, Diego Moura; Silva, Ângela; Lipscomb, Michael W.; Borges, Valéria M.; Jesus, Amélia Ribeiro de; Almeida, Roque Pacheco de; Moura, Tatiana Rodrigues de

doi:10.3389/fmicb.2017.02265

Cited by 16 publications

(20 citation statements)

References 28 publications

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“…Studies have explored the role of TREM-1 in inducing inflammation in multiple contexts, such as sepsis [9,21], cancer [22], viral infections [23,24], and others non-infectious diseases [25,26]. However, the role of TREM-1 signaling in innate immunity against parasite infections and its underlying mechanisms remain unknown [13,27,28].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, neutrophils infected by L. infantum enhance the transcription of TREM-1 and molecules associated with its activation as well as the release of sTREM-1. Both were associated with clinical parameters of visceral leishmaniasis severity, suggesting that the release of sTREM-1 inhibits inflammation and favors disease development by impairing TREM-1 signaling [13].…”

Section: Discussionmentioning

confidence: 99%

Section: Validation Of Differentially Expressed Genes From Trem-1 Pathway In Active Lesions Of CLmentioning

confidence: 99%

“…Although the expression of TREM-1 and sTREM-1 (soluble form) has been demonstrated during the infection of different Leishmania species, the activation of the TREM-1 pathway in Cl lesions caused by Lb remains undetermined [6,[11][12][13]20]. To validate the activation of the TREM-1 pathway in CL, some genes were selected based on their role within the pathway, such as receptors the TREM-1 and TLR2, the adaptor protein DAP12 (coded by TYROBP gene) and the product DEFB4A.…”

Section: Validation Of Differentially Expressed Genes From Trem-1 Pathway In Active Lesions Of CLmentioning

confidence: 99%

“…It has already been demonstrated that human neutrophils infected in vitro with L. infantum upregulate the expression of TREM-1, DAP-12, and IL-8. In addition, increased serum levels of the soluble form of TREM-1 (sTREM-1) were associated with the severity of visceral leishmaniasis (VL) [13]. Neutrophil recruitment to CL lesions has also been associated with TREM-1 in experimental models.…”

Section: Introductionmentioning

confidence: 99%

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Keratinocytes and Activation of TREM-1 Pathway in Cutaneous Leishmaniasis Lesions

Nunes

Ampuero

Bonyek-Silva

et al. 2021

Microbiology Research

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Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) amplifies the immune response, operating synergistically with Toll-Like Receptors (TLRs) in the production of inflammatory mediators. TREM-1 signaling depends on the adapter protein DAP12, which results in the activation of NFkB, the expression of inflammatory genes, and the release of antimicrobial peptides, such as Beta-defensin 2. We evaluated the activation of the TREM-1 signaling pathways in Cutaneous Leishmaniasis (CL) caused by Leishmania braziliensis and linage human keratinocytes exposed to these parasites since the host immune response against Leishmania plays a critical role in promoting parasite killing but also participates in inflammation and tissue damage. We analyzed publicly available transcriptome data from the lesions of CL patients. In the CL biopsies, we found increased expression of the molecules involved in the TREM-1 pathway. We then validated these findings with RT-qPCR and immunohistochemistry in newly obtained biopsies. Surprisingly, we found a strong labeling of TREM-1 in keratinocytes, prompting the hypothesis that increased TREM-1 activation may be the result of tissue damage. However, increased TREM-1 expression was only seen in human lineage keratinocytes following parasite stimulation. Moreover, no up-regulation of TREM-1 expression was observed in the skin lesions caused by other non-infectious inflammatory diseases. Together, these findings indicate that L. braziliensis (Lb) induces the expression of the TREM-1 receptor in tissue keratinocytes regardless of tissue damage, suggesting that non-immune skin cells may play a role in the inflammatory response of CL.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Validation Of Differentially Expressed Genes From Trem-1 Pathway In Active Lesions Of CLmentioning

confidence: 99%

Section: Validation Of Differentially Expressed Genes From Trem-1 Pathway In Active Lesions Of CLmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Keratinocytes and Activation of TREM-1 Pathway in Cutaneous Leishmaniasis Lesions

Nunes

Ampuero

Bonyek-Silva

et al. 2021

Microbiology Research

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Neutrophils and Visceral Leishmaniasis: Impact on innate immune response and cross‐talks with macrophages and dendritic cells

Kupani

Pandey²,

Mehrotra

2020

Journal Cellular Physiology

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Neutrophils with their array of microbicidal activities are the first innate immune cells to guard against infection. They are also most crucial for the host's initial defense against Leishmania parasites which cause clinically diverse diseases ranging from self‐healing cutaneous leishmaniasis (CL) to a more severe visceral form, visceral leishmaniasis (VL). Neutrophils are recruited in large numbers at the infection site after bite of sandfly, which is the vector for the disease. The initial interaction of neutrophils with the parasites may modulate the subsequent innate and adaptive immune responses and hence affect the disease outcome. The purpose of this review is to comprehensively appraise the role of neutrophils during the early stages of Leishmania infection with a focus on the visceral form of the disease. In the past decade, new insights regarding the role of neutrophils in VL have surfaced which have been extensively elaborated in the present review. In addition, since much of the information regarding neutrophil–Leishmania early interaction has accumulated through studies on mouse models of CL, these studies are also revisited. We begin by reviewing the factors which drive the recruitment of neutrophils at the site of injection by the sandfly. We then discuss the studies delineating the molecular mechanisms involved in the uptake of the Leishmania parasite by neutrophils and how the parasite subverts their microbicidal functions. In the end, the interaction of infected neutrophils with macrophages and dendritic cells is summarized.

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Role of triggering receptor expressed on myeloid cells-1 (TREM-1) in COVID-19 and other viral pneumonias: a systematic review and meta-analysis of clinical studies

et al. 2022

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Background Triggering receptor expressed on myeloid cells-1 (TREM-1) has emerged as an important inflammatory marker of immune response associated with severity and mortality outcomes in infection diseases, including viral pneumonias. Aim (1) To evaluate the expression of TREM-1 in patients with COVID-19 and other viral pneumonias compared to healthy individuals; and (2) to analyze the levels of these biomarkers according to disease severity. Materials and methods This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Searches were performed in PubMed, Scopus, Embase, and Google Scholar. Studies were considered eligible if they were observational studies that provided data on the levels of TREM-1 in humans with viral pneumonia compared to healthy controls. The results of the meta-analysis were expressed as standardized mean difference (SMD) and an effect size of 0.8 was considered a large effect. A subgroup analysis was performed according to the disease severity. Results Seven studies were included in this systematic review. Four studies included patients with COVID-19 and three analyzed patients with different viruses. The meta-analysis was performed only with patients with COVID-19, which showed increased levels of soluble form of TREM-1 (sTREM-1) among patients with COVID-19 compared to healthy controls (SMD 1.53; 95% CI 0.53–2.52; p < 0.01). No differences were found between patients with mild-to-moderate COVID-19 and healthy controls, but higher levels of sTREM-1 were shown among patients with severe COVID-19 (SMD 1.83; 95% CI 0.77–2.88; p < 0.01). All three studies including patients with other viral pneumonias showed that TREM-1 levels were significantly elevated in infected patients compared with controls. Conclusion These findings may provide evidence on the pro-inflammatory role of TREM-1 in these infections, contributing to the inflammatory profile and disease progression. Supplementary Information The online version contains supplementary material available at 10.1007/s10787-022-00972-6.

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Leishmania infantum Induces the Release of sTREM-1 in Visceral Leishmaniasis

Cited by 16 publications

References 28 publications

Keratinocytes and Activation of TREM-1 Pathway in Cutaneous Leishmaniasis Lesions

Keratinocytes and Activation of TREM-1 Pathway in Cutaneous Leishmaniasis Lesions

Neutrophils and Visceral Leishmaniasis: Impact on innate immune response and cross‐talks with macrophages and dendritic cells

Role of triggering receptor expressed on myeloid cells-1 (TREM-1) in COVID-19 and other viral pneumonias: a systematic review and meta-analysis of clinical studies

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