title: IgA modulates respiratory dysfunction as a sequela to pulmonary chlamydial infection as neonates.
abstract: Neonatal Chlamydia lung infections are associated with serious sequelae such as asthma and airway hyper-reactivity in children and adults. Our previous studies demonstrated the importance of Th-1 type cytokines, IL-12 and IFN-γ in protection against neonatal pulmonary chlamydial challenge; however, the role of the humoral arm of defense has not been elucidated. We hypothesized that B-cells and IgA, the major mucosal antibody, play a protective role in newborns against development of later life respiratory sequelae to Chlamydia infection. Our studies using neonatal mice revealed that all WT and IgA-deficient (IgA(-/-)) animals survived a sublethal pulmonary Chlamydia muridarum challenge at one day after birth with similar reduction in bacterial burdens over time. In contrast, all B-cell-deficient (μMT) mice succumbed to infection at the same challenge dose correlating to failure to control bacterial burdens in the lungs. Although IgA may not be important for bacterial clearance, we observed IgA(-/-) mice displayed greater respiratory dysfunction 5 weeks post challenge. Specifically, comparative respiratory functional analyses revealed a significant shift upward in P-V loops, and higher dynamic resistance in IgA(-/-) animals. This study provides insight(s) into the protective role of IgA in neonates against pulmonary chlamydial infection induced respiratory pathological sequelae observed later in life.
authors.affiliation: Department of Biology, The South Texas Center for Emerging Infectious Diseases, and the Center for Excellence in Infection Genomics, University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA.
authors.forename: Gopala Krishna Koundinya
authors.initials: GK
authors.lastname: Lanka
authors.affiliation: Department of Biology, The South Texas Center for Emerging Infectious Diseases, and the Center for Excellence in Infection Genomics, University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA.
authors.forename: Jieh-Juen
authors.initials: JJ
authors.lastname: Yu
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Siqi
authors.initials: S
authors.lastname: Gong
authors.affiliation: Department of Biology, The South Texas Center for Emerging Infectious Diseases, and the Center for Excellence in Infection Genomics, University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA.
authors.forename: Rishein
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Department of Pediatrics, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Shamimunisa B
authors.initials: SB
authors.lastname: Mustafa
authors.affiliation: Department of Pathology, Midwestern University, 555 31st Street, Downers Grove, IL 60515, USA.
authors.forename: Ashlesh K
authors.initials: AK
authors.lastname: Murthy
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
authors.affiliation: Department of Biology, The South Texas Center for Emerging Infectious Diseases, and the Center for Excellence in Infection Genomics, University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Chambers
authors.affiliation: Department of Biology, The South Texas Center for Emerging Infectious Diseases, and the Center for Excellence in Infection Genomics, University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA.
authors.forename: M Neal
authors.initials: MN
authors.lastname: Guentzel
authors.affiliation: Department of Biology, The South Texas Center for Emerging Infectious Diseases, and the Center for Excellence in Infection Genomics, University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA bernard.arulanandam@utsa.eu.
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Arulanandam
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000382:microbiology; D001402:B-Lymphocytes / Q000276:immunology; D002690:Chlamydia Infections / Q000235:genetics / Q000276:immunology*; D023502:Chlamydia muridarum / Q000276:immunology*; D007070:Immunoglobulin A / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D037662:Pulmonary Surfactant-Associated Protein A / Q000032:analysis / Q000096:biosynthesis; D012129:Respiratory Function Tests; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D037662:Pulmonary Surfactant-Associated Protein A; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: Chlamydia trachomatis; IgA; histopathology; neonate; respiratory; surfactant