RATIONALE: Recurrent wheeze and asthma are thought to result from alterations in early life immune development following respiratory syncytial virus (RSV) infection. However, prior studies of the nasal immune response to infection have assessed only individual cytokines, which does not capture the whole spectrum of response to infection. OBJECTIVES: To identify nasal immune phenotypes in response to RSV infection and their association with recurrent wheeze. METHODS: A birth cohort of term healthy infants born June to December were recruited and followed to capture the first infant RSV infection. Nasal wash samples were collected during acute respiratory infection, viruses were identified by RT-PCR, and immune-response analytes were assayed using a multianalyte bead-based panel. Immune-response clusters were identified using machine learning, and association with recurrent wheeze at age 1 and 2 years was assessed using logistic regression. MEASUREMENTS AND MAIN RESULTS: We identified two novel and distinct immune-response clusters to RSV and human rhinovirus. In RSV-infected infants, a nasal immune-response cluster characterized by lower non-IFN antiviral immune-response mediators, and higher type-2 and type-17 cytokines was significantly associated with first and second year recurrent wheeze. In comparison, we did not observe this in infants with human rhinovirus acute respiratory infection. Based on network analysis, type-2 and type-17 cytokines were central to the immune response to RSV, whereas growth factors and chemokines were central to the immune response to human rhinovirus. CONCLUSIONS: Distinct immune-response clusters during infant RSV infection and their association with risk of recurrent wheeze provide insights into the risk factors for and mechanisms of asthma development.
RATIONALE: Recurrent wheeze and asthma are thought to result from alterations in early life immune development following respiratory syncytial virus (RSV) infection. However, prior studies of the nasal immune response to infection have assessed only individual cytokines, which does not capture the whole spectrum of response to infection. OBJECTIVES: To identify nasal immune phenotypes in response to RSV infection and their association with recurrent wheeze. METHODS: A birth cohort of term healthy infants born June to December were recruited and followed to capture the first infantRSV infection. Nasal wash samples were collected during acute respiratory infection, viruses were identified by RT-PCR, and immune-response analytes were assayed using a multianalyte bead-based panel. Immune-response clusters were identified using machine learning, and association with recurrent wheeze at age 1 and 2 years was assessed using logistic regression. MEASUREMENTS AND MAIN RESULTS: We identified two novel and distinct immune-response clusters to RSV and human rhinovirus. In RSV-infectedinfants, a nasal immune-response cluster characterized by lower non-IFN antiviral immune-response mediators, and higher type-2 and type-17 cytokines was significantly associated with first and second year recurrent wheeze. In comparison, we did not observe this in infants with human rhinovirus acute respiratory infection. Based on network analysis, type-2 and type-17 cytokines were central to the immune response to RSV, whereas growth factors and chemokines were central to the immune response to human rhinovirus. CONCLUSIONS: Distinct immune-response clusters during infantRSV infection and their association with risk of recurrent wheeze provide insights into the risk factors for and mechanisms of asthma development.
Entities:
Keywords:
human rhinovirus; immune response; respiratory syncytial virus; systems approach; wheeze
Authors: J Schwarze; G Cieslewicz; A Joetham; T Ikemura; M J Mäkelä; A Dakhama; L D Shultz; M C Lamers; E W Gelfand Journal: Am J Respir Crit Care Med Date: 2000-08 Impact factor: 21.405
Authors: Julia A Wisniewski; Lyndsey M Muehling; Jacob D Eccles; Brian J Capaldo; Rachana Agrawal; Debbie-Ann Shirley; James T Patrie; Lisa J Workman; Alexander J Schuyler; Monica G Lawrence; W Gerald Teague; Judith A Woodfolk Journal: J Allergy Clin Immunol Date: 2017-09-20 Impact factor: 10.793
Authors: Amy S Feldman; Tina V Hartert; Tebeb Gebretsadik; Kecia N Carroll; Patricia A Minton; Kimberly B Woodward; Emma K Larkin; Eva Kathryn Miller; Robert S Valet Journal: Pediatr Allergy Immunol Pulmonol Date: 2015-06-01 Impact factor: 1.349
Authors: Devi Rajan; Courtney E McCracken; Hannah B Kopleman; Shuya Y Kyu; F Eun-Hyung Lee; Xiaoyan Lu; Larry J Anderson Journal: PLoS One Date: 2014-12-12 Impact factor: 3.240
Authors: Asuncion Mejias; Blerta Dimo; Nicolas M Suarez; Carla Garcia; M Carmen Suarez-Arrabal; Tuomas Jartti; Derek Blankenship; Alejandro Jordan-Villegas; Monica I Ardura; Zhaohui Xu; Jacques Banchereau; Damien Chaussabel; Octavio Ramilo Journal: PLoS Med Date: 2013-11-12 Impact factor: 11.069
Authors: Christian Rosas-Salazar; Zheng-Zheng Tang; Meghan H Shilts; Kedir N Turi; Qilin Hong; Derek A Wiggins; Christian E Lynch; Tebeb Gebretsadik; James D Chappell; R Stokes Peebles; Larry J Anderson; Suman R Das; Tina V Hartert Journal: J Allergy Clin Immunol Date: 2021-09-14 Impact factor: 14.290
Authors: Steven M Brunwasser; George M Slavich; Dawn C Newcomb; Tebeb Gebretsadik; Kedir N Turi; Cosby Stone; Larry J Anderson; Tina V Hartert Journal: Brain Behav Immun Date: 2018-12-11 Impact factor: 7.217
Authors: Yoshihiko Raita; Marcos Pérez-Losada; Robert J Freishtat; Brennan Harmon; Jonathan M Mansbach; Pedro A Piedra; Zhaozhong Zhu; Carlos A Camargo; Kohei Hasegawa Journal: Nat Commun Date: 2021-06-14 Impact factor: 17.694
Authors: Sébastien A Felt; Yan Sun; Agnieszka Jozwik; Allan Paras; Maximillian S Habibi; David Nickle; Larry Anderson; Emna Achouri; Kristen A Feemster; Ana María Cárdenas; Kedir N Turi; Meiping Chang; Tina V Hartert; Shaon Sengupta; Christopher Chiu; Carolina B López Journal: Nat Microbiol Date: 2021-04-01 Impact factor: 30.964