Role of granulysin in immunity to leprosy

Ochoa, María Teresa; Thoma-Uszynski, Sybille; Sieling, Peter A.; Sabet, Shereen; Cho, S.; Krensky, Alan M.; Burdick, Anne E.; Rea, T. H.; Modlin, R L

doi:10.5935/0305-7518.20000081

Cited by 6 publications

(4 citation statements)

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“…Previous studies have demonstrated that the perforin and granulysin produced by CD8 + T cells mediate antimicrobial activity against intracellular M. tuberculosis . The role of cytolytic granules in ML antimicrobial activity has also been described . In this connection, the present study showed that purified lymphocytes lead to an increased percentage of cell death in ML‐stimulated RR/HIV cultures, suggesting an important role for T cells in the viability of the monocytic culture in RR/HIV patients.…”

Section: Discussionsupporting

confidence: 71%

Role of CD8⁺ T cells in triggering reversal reaction in HIV/leprosy patients

et al. 2013

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Summary It has been reported that the initiation of highly active anti‐retroviral therapy (HAART) is associated with the development of reversal reaction (RR) in co‐infected HIV/leprosy patients. Nevertheless, the impact of HIV and HAART on the cellular immune response to Mycobacterium leprae (ML) remains unknown. In the present study, we observed that ex vivo peripheral blood mononuclear cells (PBMCs) of both RR and RR/HIV patients presented increased percentages of activated CD4+ T cells when compared with the healthy individuals (HC) group. The frequency of CD8+ CD38+ cells increased in the PBMCs of RR/HIV patients but not in RR patients when compared with the HC group. Both RR and RR/HIV skin lesion cells presented similar percentages of activated CD4+ cells, but the numbers of activated CD8+ cells were higher in RR/HIV in comparison to the RR group. The frequency of interferon‐γ‐producing cells was high in response to ML regardless of HIV co‐infection. In ML‐stimulated cells, there was an increase in central memory CD4+ T‐cell frequencies in the RR and RR/HIV groups, but an increase in central memory CD8+ T‐cell frequency was only observed in the RR/HIV group. ML increased granzyme B+ effector memory CD8+ T‐cell frequencies in the RR/HIV PBMCs, but not in the HC and RR groups. Our data suggest that the increased expression of effector memory CD8+ T cells, together with greater perforin/granzyme B production, could be an additional mechanism leading to the advent of RR in co‐infected patients. Moreoever, this increased expression may explain the severity of RR occurring in these patients.

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Section: Discussionsupporting

confidence: 71%

Role of CD8⁺ T cells in triggering reversal reaction in HIV/leprosy patients

et al. 2013

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“…Other studies involving granulysin mediated antimicrobial activities provided additional insights. Perhaps most revealing were studies of the causative agent of leprosy, M. leprae (14,17). Leprosy may be either tuberculoid, forming granulomas, or disseminated, referred to as lepromatous.…”

Section: Introductionmentioning

confidence: 99%

“…Leprosy may be either tuberculoid, forming granulomas, or disseminated, referred to as lepromatous. Granulysin expression is high in granulomatous lesions and low in the disseminated form, showing for the first time that granulysin expression correlates with clinical status in an infectious disease (14,17). Of particular interest, granulysin was expressed in CD4+ T cells in the lepromatous granulomas, while perforin was expressed in CD8+ T cells, suggesting the interesting hypothesis that, if both granulysin and perforin were expressed in the same cell, perhaps no disease would occur.…”

Section: Introductionmentioning

confidence: 99%

Granulysin: A Novel Host Defense Molecule

Krensky

Clayberger

2005

American Journal of Transplantation

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“…Through activation via TLRs and secretion of IFN-g, the innate and adaptive immune systems trigger the vitamin D-dependent induction of the antimicrobial proteins encoded by CAMP and DEFB4A (Fabri et al, 2011;Liu et al, 2006;Montoya et al, 2009). T cells release antimicrobial proteins encoded by GNLY and IL26, which can enter infected macrophages and exert a direct antimicrobial activity (Dang et al, 2019;Ochoa et al, 2000;Stenger et al, 1998;Stenger et al, 1997). These human pathways are not present in mice, which utilize other mechanisms such as the release of nitric oxide to kill mycobacteria.…”

Section: Introductionmentioning

confidence: 99%

Single Cell and Spatial Transcriptomics Defines the Cellular Architecture of the Antimicrobial Response Network in Human Leprosy Granulomas

Hughes

Teles

et al. 2020

Preprint

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Granulomas are complex cellular structures comprised predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated single cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RR), a dynamic process in which some patients with disseminated lepromatous leprosy (L-lep) transition towards self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions, and regulated by IFN-g and IL1-b. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts contribute to the antimicrobial response.

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Role of granulysin in immunity to leprosy

Cited by 6 publications

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Role of CD8⁺ T cells in triggering reversal reaction in HIV/leprosy patients

Role of CD8⁺ T cells in triggering reversal reaction in HIV/leprosy patients

Granulysin: A Novel Host Defense Molecule

Single Cell and Spatial Transcriptomics Defines the Cellular Architecture of the Antimicrobial Response Network in Human Leprosy Granulomas

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Role of granulysin in immunity to leprosy

Cited by 6 publications

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Role of CD8+ T cells in triggering reversal reaction in HIV/leprosy patients

Role of CD8+ T cells in triggering reversal reaction in HIV/leprosy patients

Granulysin: A Novel Host Defense Molecule

Single Cell and Spatial Transcriptomics Defines the Cellular Architecture of the Antimicrobial Response Network in Human Leprosy Granulomas

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Product

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Role of CD8⁺ T cells in triggering reversal reaction in HIV/leprosy patients

Role of CD8⁺ T cells in triggering reversal reaction in HIV/leprosy patients