title: Differential expression of alpha 4 integrins on effector memory T helper cells during Bordetella infections. Delayed responses in Bordetella pertussis.
abstract: Bordetella pertussis (B. pertussis) is the causative agent of whooping cough, a respiratory disease that is reemerging worldwide. Mechanisms of selective lymphocyte trafficking to the airways are likely to be critical in the immune response to this pathogen. We compared murine infection by B. pertussis, B. parapertussis, and a pertussis toxin-deleted B. pertussis mutant (BpΔPTX) to test the hypothesis that effector memory T-helper cells (emTh) display an altered pattern of trafficking receptor expression in B. pertussis infection due to a defect in imprinting. Increased cell recruitment to the lungs at 5 days post infection (p.i.) with B. parapertussis, and to a lesser extent with BpΔPTX, coincided with an increased frequency of circulating emTh cells expressing the mucosal-associated trafficking receptors α4β7 and α4β1 while a reduced population of these cells was observed in B. pertussis infection. These cells were highly evident in the blood and lungs in B. pertussis infection only at 25 days p.i. when B. parapertussis and BpΔPTX infections were resolved. Although at 5 days p.i., an equally high percentage of lung dendritic cells (DCs) from all infections expressed maturation markers, this expression persisted only in B. pertussis infection at 25 days p.i. Furthermore, at 5 days p.i with B. pertussis, lung DCs migration to draining lymph nodes may be compromised as evidenced by decreased frequency of CCR7(+) DCs, inhibited CCR7-mediated in vitro migration, and fewer DCs in lung draining lymph nodes. Lastly, a reduced frequency of allogeneic CD4(+) cells expressing α4β1 was detected following co-culture with lung DCs from B. pertussis-infected mice, suggesting a defect in DC imprinting in comparison to the other infection groups. The findings in this study suggest that B. pertussis may interfere with imprinting of lung-associated trafficking receptors on T lymphocytes leading to extended survival in the host and a prolonged course of disease.
authors.affiliation: Department of Biology, San Jose State University, San Jose, California, United States of America.
authors.forename: Tuan M
authors.initials: TM
authors.lastname: Nguyen
authors.forename: Dipti
authors.initials: D
authors.lastname: Ravindra
authors.forename: Brian
authors.initials: B
authors.lastname: Kwong
authors.forename: Sana
authors.initials: S
authors.lastname: Waheed
authors.forename: Ryan
authors.initials: R
authors.lastname: Ferguson
authors.forename: Nicole
authors.initials: N
authors.lastname: Tarlton
authors.forename: Victoria
authors.initials: V
authors.lastname: Wu
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Sequeira
authors.forename: Martina
authors.initials: M
authors.lastname: Bremer
authors.forename: Tzvia
authors.initials: T
authors.lastname: Abramson
mesh_terms: D000818:Animals; D001885:Bordetella Infections / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D042483:Bordetella parapertussis; D001886:Bordetella pertussis; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D005260:Female; D039441:Integrin alpha4 / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism* / Q000473:pathology
chemical_list: D039441:Integrin alpha4