Differential susceptibility and maturation of thymocyte subsets during Salmonella Typhimurium infection: insights on the roles of glucocorticoids and Interferon-gamma

Majumdar, Shamik and Deobagkar-Lele, Mukta and Adiga, Vasista and Raghavan, Abinaya and Wadhwa, Nitin and Ahmed, Syed Moiz and Rananaware, Supriya Rajendra and Chakraborty, Subhashish and Joy, Omana and Nandi, Dipankar (2017) Differential susceptibility and maturation of thymocyte subsets during Salmonella Typhimurium infection: insights on the roles of glucocorticoids and Interferon-gamma. In: SCIENTIFIC REPORTS, 7 .

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Abstract

The thymus is known to atrophy during infections; however, a systematic study of changes in thymocyte subpopulations has not been performed. This aspect was investigated, using multi-color flow cytometry, during oral infection of mice with Salmonella Typhimurium (S. Typhimurium). The major highlights are: First, a block in the developmental pathway of CD4(-)CD8(-) double negative (DN) thymocytes is observed. Second, CD4(+)CD8(+) double positive (DP) thymocytes, mainly in the DP1 (CD5(lo)CD3(lo)) and DP2 (CD5(hi)CD3(int)), but not DP3 (CD5(int)CD3(hi)), subsets are reduced. Third, single positive (SP) thymocytes are more resistant to depletion but their maturation is delayed, leading to accumulation of CD24(hi)CD3(hi) SP. Kinetic studies during infection demonstrated differences in sensitivity of thymic subpopulations: Immature single positive (ISP) > DP1, DP2 > DN3, DN4 > DN2 > CD4(+) > CD8(+). Upon infection, glucocorticoids (GC), inflammatory cytokines, e.g. Ifn gamma, etc are induced, which enhance thymocyte death. Treatment with RU486, the GC receptor antagonist, increases the survival of most thymic subsets during infection. Studies with Ifn gamma(-/-) mice demonstrated that endogenous Ifn gamma produced during infection enhances the depletion of DN2-DN4 subsets, promotes the accumulation of DP3 and delays the maturation of SP thymocytes. The implications of these observations on host cellular responses during infections are discussed.

Item Type:	Journal Article
Publication:	SCIENTIFIC REPORTS
Additional Information:	Copy right for this article belongs to the NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	16 Feb 2017 06:37
Last Modified:	23 Oct 2018 14:46
URI:	http://eprints.iisc.ac.in/id/eprint/56239

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