IgA deficiency potentiates altered respiratory function following neonatal pulmonary chlamydial infection

Neonatal Chlamydia lung infections are associated with serious sequelae such as asthma and airway hyperreactivity (AHR) in children and adults. However, the role of B-cells and the major mucosal antibody IgA in pathogenesis have not been modeled. Objectives: We hypothesize that B-cells and antibodies play a protective role against development of later life serious respiratory sequelae to Chlamydia infection of newborns. One day old pups of wild type (WT), B-cell-/- (μMT) and IgA-/- C57BL/6 mice were challenged intranasally (i.n.) with 100 IFUs of C. muridarum and monitored 30 days for morbidity and mortality. Chlamydial burdens in lungs, liver and spleen were assessed on days 4, 7, 10, 14 and 18 post-challenge (PC). Anti- Chlamydia serum IgG titers were determined on days 15 and 30 PC. Lung functions were analyzed at 5 weeks PC using the FlexiVent system. All B-cell-/- animals succumbed to the pulmonary chlamydial infection by 30 days PC while all WT and IgA-/- animals survived. Additionally, comparable Chlamydia burdens and dissemination profiles observed between WT and IgA-/- animals was coincident with comparable total antigen-specific IgG, suggesting that while B cells were essential in protection against pulmonary neonatal Chlamydia infection, IgA was dispensable. However, comparative respiratory functional analysis revealed a significant shift upward in P-V loops and higher dynamic resistance in IgA-/- animals, suggesting that IgA might play a protective role in alleviating respiratory pathological sequelae. B-cells protect against chlamydial neonatal infection and IgA plays a protective role against later life serious respiratory sequelae; the basis of this protection is being investigated.