Chlamydia muridarum Lung Infection in Infants Alters Hematopoietic Cells to Promote Allergic Airway Disease in Mice

Abstract

BackgroundViral and bacterial respiratory tract infections in early-life are linked to the development of allergic airway inflammation and asthma. However, the mechanisms involved are not well understood. We have previously shown that neonatal and infant, but not adult, chlamydial lung infections in mice permanently alter inflammatory phenotype and physiology to increase the severity of allergic airway disease by increasing lung interleukin (IL)-13 expression, mucus hyper-secretion and airway hyper-responsiveness. This occurred through different mechanisms with infection at different ages. Neonatal infection suppressed inflammatory responses but enhanced systemic dendritic cell:T-cell IL-13 release and induced permanent alterations in lung structure (i.e., increased the size of alveoli). Infant infection enhanced inflammatory responses but had no effect on lung structure. Here we investigated the role of hematopoietic cells in these processes using bone marrow chimera studies.Methodology/Principal FindingsNeonatal (<24-hours-old), infant (3-weeks-old) and adult (6-weeks-old) mice were infected with C. muridarum. Nine weeks after infection bone marrow was collected and transferred into recipient age-matched irradiated naïve mice. Allergic airway disease was induced (8 weeks after adoptive transfer) by sensitization and challenge with ovalbumin. Reconstitution of irradiated naïve mice with bone marrow from mice infected as neonates resulted in the suppression of the hallmark features of allergic airway disease including mucus hyper-secretion and airway hyper-responsiveness, which was associated with decreased IL-13 levels in the lung. In stark contrast, reconstitution with bone marrow from mice infected as infants increased the severity of allergic airway disease by increasing T helper type-2 cell cytokine release (IL-5 and IL-13), mucus hyper-secretion, airway hyper-responsiveness and IL-13 levels in the lung. Reconstitution with bone marrow from infected adult mice had no effects.ConclusionsThese results suggest that an infant chlamydial lung infection results in long lasting alterations in hematopoietic cells that increases the severity of allergic airway disease in later-life.

Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction

“…These could involve other systemic responses such as conditioning of the BM, widespread and transportable inflammatory factors such as microRNAs and inflammasomes/ASC specks could be involved, and events may be exaggerated by infectious exacerbations of pulmonary disease (16,(71)(72)(73). These potential pathogenic processes could be examined using combinations of animal models and clinical studies.…”

Distribution of pathogens causing nosocomial infection in patients with bronchial asthma

“…In addition, some researchers observed that C. pneumoniae can induce asthma (Horvat et al, 2010a(Horvat et al, , 2010bStarkey et al, 2012). It has been reported (Jahnsen et al, 2006;Ahmed et al, 2007;Goleva et al, 2008) that NRI-induced asthma may be associated with neural regulatory mechanisms.…”

Programming of the Lung in Early Life by Bacterial Infections Predisposes to Chronic Respiratory Disease

“…13 Reconstitution of irradiated naive BALB/c mice with bone marrow from mice infected as infants also increased the severity of AAD by increasing mucus hypersecretion, AHR, and IL-13 levels in the lung. 45 Reconstitution with bone marrow from infected adult mice had no effects. 45 Therefore, infant infection-induced alterations in hematopoietic cells may play a previously unrecognized role in predisposing to severe AAD in later life.…”

“…45 Reconstitution with bone marrow from infected adult mice had no effects. 45 Therefore, infant infection-induced alterations in hematopoietic cells may play a previously unrecognized role in predisposing to severe AAD in later life.…”