title: Differential susceptibility and maturation of thymocyte subsets during Salmonella Typhimurium infection: insights on the roles of glucocorticoids and Interferon-gamma.
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 (CD5loCD3lo) and DP2 (CD5hiCD3int), but not DP3 (CD5intCD3hi), subsets are reduced. Third, single positive (SP) thymocytes are more resistant to depletion but their maturation is delayed, leading to accumulation of CD24hiCD3hiSP. 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. Ifnγ, 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 Ifnγ-/-mice demonstrated that endogenous Ifnγ 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.
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Shamik
authors.initials: S
authors.lastname: Majumdar
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Mukta
authors.initials: M
authors.lastname: Deobagkar-Lele
authors.affiliation: Centre for Infectious Disease Research, Indian Institute of Science, Bangalore 560012, India.|Flow Cytometry Facility, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Vasista
authors.initials: V
authors.lastname: Adiga
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Abinaya
authors.initials: A
authors.lastname: Raghavan
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Wadhwa
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Syed Moiz
authors.initials: SM
authors.lastname: Ahmed
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Supriya Rajendra
authors.initials: SR
authors.lastname: Rananaware
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Subhashish
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Flow Cytometry Facility, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Omana
authors.initials: O
authors.lastname: Joy
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.|Centre for Infectious Disease Research, Indian Institute of Science, Bangalore 560012, India.|Flow Cytometry Facility, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Dipankar
authors.initials: D
authors.lastname: Nandi
mesh_terms: D000818:Animals; D001284:Atrophy; D015415:Biomarkers; D002454:Cell Differentiation / Q000276:immunology; D004198:Disease Susceptibility; D005938:Glucocorticoids / Q000378:metabolism*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism*; D018655:Lymphocyte Count; D051379:Mice; D012480:Salmonella Infections / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D012486:Salmonella typhimurium / Q000502:physiology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D007371:Interferon-gamma