The Contribution of the Fas/FasL Apoptotic Pathway in Ulcer Formation during Leishmania major-Induced Cutaneous Leishmaniasis

Eidsmo, Liv; Nylén, Susanne; Khamesipour, Ali; Hedblad, Mari‐Anne; Chiodi, Francesca; Akuffo, Hannah

doi:10.1016/s0002-9440(10)62330-9

Cited by 30 publications

(44 citation statements)

References 43 publications

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“…79 En las lesiones de pacientes con LC infectados con L. major se detectó sobreexpresión de FasL en macrófagos y linfocitos T activados, en nexo con expresión de Fas; empero, se vinculó con la formación de la úlcera, ya que se encontró un buen número de queratinocitos en apoptosis. 80 También se ha informado una correlación entre la citotoxicidad in vitro de linfocitos de sangre periférica de pacientes con LC contra macrófagos infectados con L. major y la liberación de granzima B. 72 Toda la evidencia señala la participación de la citotoxicidad en la reacción inmunitaria específica y parece relacionarse con la curación.…”

Section: Degradación De Leishmaniaunclassified

Linfocitos T citotóxicos CD8+ en la leishmaniasis cutánea

Hernández-Ruiz¹,

Becker²

2006

Salud pública Méx

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Section: Degradación De Leishmaniaunclassified

Linfocitos T citotóxicos CD8+ en la leishmaniasis cutánea

Hernández-Ruiz¹,

Becker²

2006

Salud pública Méx

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“…1 However, some of the results obtained in this context indicated that Fas pathway may not be the only player involved in apoptosis of keratinocytes during CL. For example, when soluble FasL (sFasL)-containing supernatants from restimulated CL peripheral blood mononuclear cells (PBMCs) were used to induce apoptosis in human keratinocytes, blocking of the Fas/ FasL pathway inhibited apoptosis only in two thirds of the analyzed supernatants.…”

mentioning

confidence: 92%

“…At the site of the ulcer, in the dermis of the skin, L. majorinfected macrophages and infiltrating, activated T cells, monocytes, neutrophils, and plasma cells are found. We 1 and others 2,3 have suggested a role for Fas apoptosis mediated by its natural ligand (FasL) in ulcer formation and parasite clearance during CL.…”

mentioning

confidence: 96%

FasL and TRAIL Induce Epidermal Apoptosis and Skin Ulceration Upon Exposure to Leishmania major

Eidsmo

Fluur

Réthi

et al. 2007

The American Journal of Pathology

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Receptor-mediated apoptosis is proposed as an important regulator of keratinocyte homeostasis in human epidermis. We have previously reported that Fas/FasL interactions in epidermis are altered during cutaneous leishmaniasis (CL) and that keratinocyte death through apoptosis may play a pathogenic role for skin ulceration. To further investigate the alterations of apoptosis during CL, a keratinocyte cell line (HaCaT) and primary human epidermal keratinocytes were incubated with supernatants from Leishmania major-infected peripheral blood mononuclear cells. An apoptosis-specific microarray was used to assess mRNA expression in HaCaT cells exposed to supernatants derived from L. major-infected cultures. Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA and protein expression were significantly up-regulated, and apoptosis was detected in both HaCaT and human epidermal keratinocyte cells. The keratinocyte apoptosis was partly inhibited through blocking of Fas or FasL and even more efficiently through TRAIL neutralization. Up-regulation of Fas on keratinocytes in epidermis and the presence of FasL-expressing macrophages and T cells in dermis were previously reported by us. In this study, keratinocytes expressing TRAIL, as well as the proapoptotic receptor TRAIL-R2, were detected in skin biopsies from CL cases. We propose that activation of Fas and TRAIL apoptosis pathways, in the presence of inflammatory mediators at the site of infection, leads to tissue destruction and ulceration during CL. (Am J

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“…In addition, increased Fas/FasL expression was detected in cells infiltrating cutaneous lesions in murine infection [21]. Moreover, systemic neutralization of FasL and TRAIL reduces skin ulceration in experimental Leishmaniasis [22].…”

Section: Introductionmentioning

confidence: 98%

Inhibition of caspase-8 activity promotes protective Th1- and Th2-mediated immunity toLeishmania majorinfection

Pereira-Manfro

Ribeiro-Gomes

Filardy

et al. 2013

Journal of Leukocyte Biology

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We investigated how apoptosis pathways mediated by death receptors and caspase-8 affect cytokine responses and immunity to Leishmania major parasites. Splenic CD4 T cells undergo activation-induced apoptosis, and blockade of FasL-Fas interaction increased IFN-␥ and IL-4 cytokine responses to L. major antigens. To block death receptor-induced death, we used mice expressing a T cell-restricted transgene for vFLIP. Inhibition of caspase-8 activation in vFLIP mice enhanced Th1 and Th2 cytokine responses to L. major infection, even in the Th1-prone B6 background. We also observed increased NO production by splenocytes from vFLIP mice upon T cell activation. Despite an exacerbated Th2 response, vFLIP mice controlled better L. major infection, with reduced lesions and lower parasite loads compared with WT mice. Moreover, injection of anti-IL-4 mAb in infected vFLIP mice disrupted control of parasite infection. Therefore, blockade of caspase-8 activity in T cells improves immunity to L. major infection by promoting increased Th1 and Th2 responses. J. Leukoc. Biol. 95: 347-355; 2014.

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The Contribution of the Fas/FasL Apoptotic Pathway in Ulcer Formation during Leishmania major-Induced Cutaneous Leishmaniasis

Abstract: Cutaneous leishmaniasis (CL), caused by the intracellular protozoan

Cited by 30 publications

References 43 publications

Linfocitos T citotóxicos CD8+ en la leishmaniasis cutánea

Linfocitos T citotóxicos CD8+ en la leishmaniasis cutánea

FasL and TRAIL Induce Epidermal Apoptosis and Skin Ulceration Upon Exposure to Leishmania major

Inhibition of caspase-8 activity promotes protective Th1- and Th2-mediated immunity toLeishmania majorinfection

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