Keratinocyte infection by Actinomadura madurae triggers an inflammatory response

Santiago-Téllez, Alfonso; Castrillón-Rivera, Laura Estela; Palma-Ramos, Alejandro; Bello–López, Juan Manuel; Sainz‐Espuñes, Teresita; Contreras‐Paredes, Adriana; Luna-Herrera, Julieta; Castañeda‐Sánchez, Jorge Ismael

doi:10.1093/trstmh/trz022

Cited by 3 publications

(2 citation statements)

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“…Keratinocytes are among the epidermal cell lines that maintain the integrity of this barrier and tissue homeostasis [ 25 ]. In addition, when coming into contact with a microorganism, they participate by mediating antimicrobial responses, promoting a pro-inflammatory environment, and producing antimicrobial peptides in infections with actinomycetes, viruses and fungi [ 26 , 27 , 28 ]. However, information is limited on the involvement of keratinocytes in the pathogenesis of fungi such as S. schenckii .…”

Section: Discussionmentioning

confidence: 99%

Keratinocyte Response to Infection with Sporothrix schenckii

Paredes-Rojas

Palma-Ramos

Castrillón-Rivera

et al. 2022

JoF

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Sporotrichosis is a subacute, or chronic mycosis caused by traumatic inoculation of material contaminated with the fungus Sporothrix schenckii which is part of the Sporothrix spp. complex. The infection is limited to the skin, although its progression to more severe systemic or disseminated forms remains possible. Skin is the tissue that comes into contact with Sporothrix first, and the role of various cell lines has been described with regard to infection control. However, there is little information on the response of keratinocytes. In this study, we used the human keratinocyte cell line (HaCaT) and evaluated different aspects of infection from modifications in the cytoskeleton to the expression of molecules of the innate response during infection with conidia and yeast cells of Sporothrix schenckii. We found that during infection with both phases of the fungus, alterations of the actin cytoskeleton, formation of membrane protuberances, and loss of stress fibers were induced. We also observed an overexpression of the surface receptors MR, TLR6, CR3 and TLR2. Cytokine analysis showed that both phases of the fungus induced the production of elevated levels of the chemokines MCP-1 and IL-8, and proinflammatory cytokines IFN-α, IFN-γ and IL-6. In contrast, TNF-α production was significant only with conidial infection. In late post-infection, cytokine production was observed with immunoregulatory activity, IL-10, and growth factors, G-CSF and GM-CSF. In conclusion, infection of keratinocytes with conidia and yeast cells of Sporothrix schenckii induces an inflammatory response and rearrangements of the cytoskeleton.

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Section: Discussionmentioning

confidence: 99%

Keratinocyte Response to Infection with Sporothrix schenckii

Paredes-Rojas

Palma-Ramos

Castrillón-Rivera

et al. 2022

JoF

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“…Keratinocytes are the major structural component of the epidermis, but emerging evidence indicates their role in the immune response [30,31]. These cells express certain PRRs, including TLRs [32][33][34][35], which is an important pathway for Leishmania recognition by phagocytic cells and parasite internalization [36][37][38]. It has been shown that keratinocytes internalize L. major or L. infantum at low levels in vitro [14], but the exact mechanism by which keratinocytes recognize and phagocyte Leishmania is still unknown.…”

Section: Discussionmentioning

confidence: 99%

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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