Increased amphiregulin expression by CD4+ T cells from individuals with asymptomatic Leishmania donovani infection. Issue 6 (27th May 2022)

• Record Type: Journal Article
• Authors: Singh, Siddharth Sankar; Chauhan, Shashi Bhushan; Ng, Susanna SS; Corvino, Dillon; de Labastida Rivera, Fabian; Engel, Jessica A; Waddell, Nic; Mukhopadhay, Pamela; Johnston, Rebecca L; Koufariotis, Lambros T; Nylen, Susanne; Prakash Singh, Om; Engwerda, Christian R; Kumar, Rajiv; Sundar, Shyam
• Is Part Of: Clinical & translational immunology. Volume 11:Issue 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-27
• Subjects: amphiregulin -- CD4+ T cell -- Leishmania donovani -- regulatory T cell -- visceral leishmaniasis; Immunologic diseases -- Periodicals; Immunology -- Periodicals; Clinical medicine -- Periodicals; Immune System Diseases -- therapy; Immunotherapy; Immunologic Factors -- therapeutic use; Translational Medical Research; Molecular Targeted Therapy; Clinical medicine; Immunologic diseases; Immunology; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 616.079
• DOI: 10.1002/cti2.1396
• Languages: English
• ISSNs: 2050-0068

Abstract

Abstract: Objectives: There is an urgent need to be able to identify individuals with asymptomatic Leishmania donovani infection, so their risk of progressing to VL and transmitting parasites can be managed. This study examined transcriptional markers expressed by CD4 + T cells that could distinguish asymptomatic individuals from endemic controls and visceral leishmaniasis (VL) patients. Methods: CD4 + T cells were isolated from individuals with asymptomatic L . donovani infection, endemic controls and VL patients. RNA was extracted and RNAseq employed to identify differentially expressed genes. The expression of one gene and its protein product during asymptomatic infection were evaluated. Results: Amphiregulin (AREG) was identified as a distinguishing gene product in CD4 + T cells from individuals with asymptomatic L. donovani infection, compared to VL patients and healthy endemic control individuals. AREG levels in plasma and antigen‐stimulated whole‐blood assay cell culture supernatants were significantly elevated in asymptomatic individuals, compared to endemic controls and VL patients. Regulatory T (Treg) cells were identified as an important source of AREG amongst CD4 + T‐cell subsets in asymptomatic individuals. Conclusion: Increased Treg cell AREG expression was identified in individuals with asymptomatic L. donovani infection, suggesting the presence of an ongoing inflammatory response in these individuals required for controlling infection and that AREG may play an important role in preventing inflammation‐induced tissue damage and subsequent disease in asymptomatic individuals. Abstract : We report the discovery of amphiregulin (AREG) as a distinguishing marker of CD4 + T cells from individuals with asymptomatic Leishmania donovani infection, compared to visceral leishmaniasis (VL) patients and healthy endemic control individuals. Thus, CD4 + T‐cell AREG is elevated during asymptomatic L . donovani infection, suggesting the presence of an ongoing inflammatory response in asymptomatic individuals required for controlling infection and that AREG may play an important role in preventing inflammation‐induced tissue damage and subsequent disease in asymptomatic individuals.