TY - JOUR
T1 - IgA modulates respiratory dysfunction as a sequela to pulmonary chlamydial infection as neonates
AU - Lanka, Gopala Krishna Koundinya
AU - Yu, Jieh Juen
AU - Gong, Siqi
AU - Gupta, Rishein
AU - Mustafa, Shamimunisa B.
AU - Murthy, Ashlesh K.
AU - Zhong, Guangming
AU - Chambers, James P.
AU - Guentzel, M. Neal
AU - Arulanandam, Bernard P.
N1 - Publisher Copyright:
© FEMS 2016. All rights reserved. For permissions, please e-mail: [email protected].
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - Chlamydia trachomatis
KW - IgA
KW - histopathology
KW - neonate
KW - respiratory
KW - surfactant
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U2 - 10.1093/femspd/ftv121
DO - 10.1093/femspd/ftv121
M3 - Article
C2 - 26755533
AN - SCOPUS:85020325161
SN - 2049-632X
VL - 74
JO - Pathogens and disease
JF - Pathogens and disease
IS - 3
ER -