Saleem Basha1, Ravinder Kaur1, Tim R Mosmann2, Michael E Pichichero1. 1. Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute and. 2. Human Immunology Center, University of Rochester Medical Center, New York.
Abstract
Background: T-helper (Th) 17 cells are important in the control of Streptococcus pneumoniae. We sought to understand the mechanism of failure of Th17 immunity resulting in S. pneumoniae infections in children <2 years old. Methods: Peripheral blood mononuclear cells (PBMCs) from infection-prone (IP) and non-IP (NIP) children 9-18 months old were examined for their responses to heat-killed S. Pneumoniae, using flow cytometry, reverse-transcription polymerase chain reaction, and enzyme-linked immunoassay. We measured cytokine production, proliferation, and differentiation of Th17 cells and the expression of transcription factors in response to S. pneumoniae. Results: PBMCs of IP children stimulated with heat-killed S. pneumoniae had significantly reduced percentages of CD4+ Th1 (interleukin2, tumor necrosis factor α) and Th17 (interleukin 17A) cells compared with NIP children. Addition of exogenous Th17-promoting cytokines (interleukin 6, 1β, and 23 and transforming growth factor β) restored CD4+ Th17 cell function in cells from IP children to levels measured in NIP children. Conclusions: Reduced Th17 responses to S. pneumoniae in PBMCs of IP children can be rescued by addition of Th17-promoting cytokines.
Background: T-helper (Th) 17 cells are important in the control of Streptococcus pneumoniae. We sought to understand the mechanism of failure of Th17 immunity resulting in S. pneumoniae infections in children <2 years old. Methods: Peripheral blood mononuclear cells (PBMCs) from infection-prone (IP) and non-IP (NIP) children 9-18 months old were examined for their responses to heat-killed S. Pneumoniae, using flow cytometry, reverse-transcription polymerase chain reaction, and enzyme-linked immunoassay. We measured cytokine production, proliferation, and differentiation of Th17 cells and the expression of transcription factors in response to S. pneumoniae. Results: PBMCs of IP children stimulated with heat-killed S. pneumoniae had significantly reduced percentages of CD4+ Th1 (interleukin2, tumornecrosis factor α) and Th17 (interleukin 17A) cells compared with NIP children. Addition of exogenous Th17-promoting cytokines (interleukin 6, 1β, and 23 and transforming growth factor β) restored CD4+ Th17 cell function in cells from IP children to levels measured in NIP children. Conclusions: Reduced Th17 responses to S. pneumoniae in PBMCs of IP children can be rescued by addition of Th17-promoting cytokines.
Authors: Alan Basset; Claudette M Thompson; Susan K Hollingshead; David E Briles; Edwin W Ades; Marc Lipsitch; Richard Malley Journal: Infect Immun Date: 2007-08-13 Impact factor: 3.441
Authors: Rajatava Basu; Sarah K Whitley; Suniti Bhaumik; Carlene L Zindl; Trenton R Schoeb; Etty N Benveniste; Warren S Pear; Robin D Hatton; Casey T Weaver Journal: Nat Immunol Date: 2015-02-02 Impact factor: 25.606
Authors: Adam K A Wright; Mathieu Bangert; Jenna F Gritzfeld; Daniela M Ferreira; Kondwani C Jambo; Angela D Wright; Andrea M Collins; Stephen B Gordon Journal: PLoS Pathog Date: 2013-03-28 Impact factor: 6.823
Authors: Mark R Alderson; Tim Murphy; Stephen I Pelton; Laura A Novotny; Laura L Hammitt; Arwa Kurabi; Jian-Dong Li; Ruth B Thornton; Lea-Ann S Kirkham Journal: Int J Pediatr Otorhinolaryngol Date: 2019-12-18 Impact factor: 1.675
Authors: Sarhad Alnajjar; Panchan Sitthicharoenchai; Jack Gallup; Mark Ackermann; David Verhoeven Journal: PLoS One Date: 2021-03-11 Impact factor: 3.240
Authors: Chikondi Peno; Dominic H Banda; Ndaru Jambo; Anstead M Kankwatira; Rose D Malamba; Theresa J Allain; Daniela M Ferreira; Robert S Heyderman; David G Russell; Henry C Mwandumba; Kondwani C Jambo Journal: J Infect Date: 2017-11-29 Impact factor: 6.072