The major goal of this proposal is to better understand immune maturation and its relationship to viral respiratory infection disease severity. Viral respiratory infections (VRI) are a significant health risk to infants. These common childhood infections, for which few therapeutics or effective vaccines exist, result in significant morbidity and mortality during the first 5 years of life. As such, VRIs are a significant public health problem impacting the quality of life of affected children and places increased societal strain in the workplace and on health care utilization. Additionally VRIs appear to have a long lasting health impact, for example in some children resulting in the development of chronic allergic diseases. Uniquely, unpublished data from MESA demonstrate significantly decreased respiratory infections during the first 2 years of life in farm children compared to non-farm children. These effects parallel published findings from around the world that farm exposures lower the risk of childhood allergies and asthma. Notably, the development of allergen sensitization and highest vulnerability to VRIs coincides with the maturation phase of the immune system, and there is evidence that farm exposures enhance development of innate immunity and T regulatory (Treg) cell function. We hypothesize that farm exposures reduce the risk of VRIs in young children by enhancing the development of innate antiviral immunity and Treg function. To test this hypothesis, we will develop a unique birth cohort study from Wisconsin farm and non-farm families within MESA. Functional assays to define innate and Treg cell maturation will be utilized in a longitudinal manner along with surveillance of VRIs and allergic sensitization. A better mechanistic understanding of how environmental exposures promote resistance to VRIs and diminish allergic diseases through effects on immune maturation will allow for development of new strategies to bring benefits of farm exposures to those who live elsewhere. In addition to addressing these research goals, this project will serve as a source of extensively characterized clinical specimens (airway epithelial cells, clinical isolates of rhinoviruses) that will enable mechanistic studies to define host-virus interactions that contribute to the severity of clinical illnesses.

Public Health Relevance

Viral respiratory infections (VRI) are ubiquitous, cause significant morbidity and mortality in early life, and effective vaccines or therapies are lacking. Farm exposures in early life appear to promote immune maturation, and we have new data to show that farm children have significantly fewer respiratory illnesses. In this proposal, we will assemble a novel birth cohort to better farm effects on immune maturation and viral respiratory illnesses. The goal of this study is to identify new targets for the treatment and prevention of VRI.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI104317-01
Application #
8469996
Study Section
Special Emphasis Panel (ZAI1-PA-I (J1))
Project Start
2013-02-01
Project End
2018-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
1
Fiscal Year
2013
Total Cost
$810,800
Indirect Cost
$212,716
Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Griggs, Theodor F; Bochkov, Yury A; Basnet, Sarmila et al. (2017) Rhinovirus C targets ciliated airway epithelial cells. Respir Res 18:84
Barkal, Layla J; Procknow, Clare L; Álvarez-García, Yasmín R et al. (2017) Microbial volatile communication in human organotypic lung models. Nat Commun 8:1770
Bjerregaard, Asger; Laing, Ingrid A; Poulsen, Nadia et al. (2017) Characteristics associated with clinical severity and inflammatory phenotype of naturally occurring virus-induced exacerbations of asthma in adults. Respir Med 123:34-41
Kloepfer, Kirsten M; Sarsani, Vishal K; Poroyko, Valeriy et al. (2017) Community-acquired rhinovirus infection is associated with changes in the airway microbiome. J Allergy Clin Immunol 140:312-315.e8
Palmenberg, Ann C (2017) Rhinovirus C, Asthma, and Cell Surface Expression of Virus Receptor CDHR3. J Virol 91:
Timm, Andrea C; Warrick, Jay W; Yin, John (2017) Quantitative profiling of innate immune activation by viral infection in single cells. Integr Biol (Camb) 9:782-791
Bashir, Hiba; Grindle, Kristine; Vrtis, Rose et al. (2017) Association of rhinovirus species with common cold and asthma symptoms and bacterial pathogens. J Allergy Clin Immunol :
Turunen, Riitta; Vuorinen, Tytti; Bochkov, Yury et al. (2017) Clinical and Virus Surveillance After the First Wheezing Episode: Special Reference to Rhinovirus A and C Species. Pediatr Infect Dis J 36:539-544
Anderson, Halie M; Lemanske Jr, Robert F; Evans, Michael D et al. (2017) Assessment of wheezing frequency and viral etiology on childhood and adolescent asthma risk. J Allergy Clin Immunol 139:692-694
Bochkov, Yury A; Gern, James E (2016) Rhinoviruses and Their Receptors: Implications for Allergic Disease. Curr Allergy Asthma Rep 16:30

Showing the most recent 10 out of 45 publications