IgA modulates respiratory dysfunction as a sequela to pulmonary chlamydial infection as neonates

• Published in: Pathogens and disease Vol. 74; no. 3; p. ftv121
• Main Authors: Lanka, Gopala Krishna Koundinya, Yu, Jieh-Juen, Gong, Siqi, Gupta, Rishein, Mustafa, Shamimunisa B., Murthy, Ashlesh K., Zhong, Guangming, Chambers, James P., Guentzel, M. Neal, Arulanandam, Bernard P.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-04-2016
• Subjects: Animals; Animals, Newborn; Antibodies, Bacterial - immunology; Asthma - immunology; Asthma - microbiology; B-Lymphocytes - immunology; Chlamydia Infections - genetics; Chlamydia Infections - immunology; Chlamydia muridarum - immunology; Immunoglobulin A - genetics; Immunoglobulin A - immunology; Interferon-gamma - immunology; Interleukin-12 - immunology; Lung - microbiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Pulmonary Surfactant-Associated Protein A - analysis; Pulmonary Surfactant-Associated Protein A - biosynthesis; Respiratory Function Tests; Respiratory Hypersensitivity - immunology; Respiratory Hypersensitivity - microbiology; Respiratory Tract Infections - immunology; Respiratory Tract Infections - microbiology; Respiratory Tract Infections - pathology; histopathology; IgA; neonate; respiratory; surfactant; Chlamydia trachomatis
• ISSN: 2049-632X; 2049-632X
• DOI: 10.1093/femspd/ftv121

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.
Although IgA is not required for chlamydial clearance following pulmonary infection, it plays an important role in prevention of subsequent lung dysfunction in adults as a sequela to the neonatal infection.
Graphical Abstract Figure.
Although IgA is not required for chlamydial clearance following pulmonary infection, it plays an important role in prevention of subsequent lung dysfunction in adults as a sequela to the neonatal infection.