Chlamydial Respiratory Infections Research Articles

Chlamydial respiratory infection in childhood and spurious immunoglobulin M.

The role of Chlamydia trachomatis was investigated in lower respiratory tract infections in 254 children. The organism was not isolated in any child but Bordetella pertussis was isolated from 65. Two of the latter and one of the remaining 189 children with negative isolation, however, had immunoglobulin M (IgM) antibodies to Chlamydia trachomatis (titers of 1:64, 1:64 and 1:128). Exhaustive absorption of the sera with bordetella antigen left the chlamydial titers unchanged, thus excluding the possibility of cross-reactivity with bordetella antigen. To determine whether nonspecific stimulation of B lymphocytes played a role, sera from 72 children with infectious mononucleosis were examined. Chlamydial IgM antibodies (greater than or equal to 1:64) were detected in 14 of these sera, significantly more often than in other acute childhood infections (p = 0.002). Serotyping showed that these antibodies had a heterogeneous specificity in different sera and a reactivity pattern suggesting they were monoclonal. The association found between chlamydial IgM antibodies and Epstein-Barr virus infection implies that there is nonspecific production of these antibodies in infectious mononucleosis, suggesting that similar nonspecific antibody production could occur in other infections. This might explain the chlamydial IgM found in children with lower respiratory tract infections in whom chlamydial infection could not be confirmed by isolation.

Chlamydial pneumonitis induced in newborn guinea pigs.

One- to three-day-old guinea pigs were inoculated intranasally with the chlamydial agent of guinea pig inclusion conjunctivitis. Physical signs of infection included a marked increase in respiration rate on days 5 to 10 of infection and radiographic evidence of pneumonia on day 6. When animals were killed at various times after infection and lung tissue was examined by histopathology, evidence of pneumonia was found beginning on day 4 and lasting as long as day 12, with maximal pathological changes on days 6 to 8. The pneumonia was generally unilateral and consisted of an acute inflammatory component in the bronchioles with granulocytes in both the lumen and the wall of the bronchioles and an interstitial and intra-alveolar mononuclear infiltrate in the parenchyma of the lung. Chlamydial antigen was detected in the bronchial epithelial cells by immunoperoxidase staining, and the guinea pig inclusion conjunctivitis organism was isolated from lung tissue on days 6 to 9. No other significant bacteria were isolated from lung tissue or seen on gram stains of lung sections. Both immunoglobulin M and immunoglobulin G serum antibodies to the guinea pig inclusion conjunctivitis agent were detected as early as day 8 and reached peak levels on day 12. The infection was apparently self-limiting. This model presents the opportunity to investigate pathophysiological and immunological aspects of chlamydial respiratory infections in a neonatal animal.

The Current Status of the Diagnosis of Chlamydial Respiratory Infections

Chlamydial pneumonitis is primarily a disease of infancy. The link between adult and infant chlamydial infections is through vertical transmission from cervically infected pregnant women. Chlamydial culture and serologic tests are described; however, specific chlamydial diagnosis can be difficult, labor intensive, and require highly trained technicians. New methods of immunologic diagnosis are currently under investigation.

Ethics and Medicine

Neutrophilic asthma is a prevalent, yet recently described phenotype of asthma. It is characterized by neutrophilic rather than eosinophilic airway inflammation and airways hyperresponsiveness (AHR) and may have an infectious origin. Chlamydial respiratory infections are associated with asthma, but how these Th1-inducing bacteria influence Th2-mediated asthma remains unknown. The effects of chlamydial infection on the development of asthma were investigated using a BALB/c mouse model of OVA-induced allergic airways disease (AAD). The effects of current and resolved <i>Chlamydia muridarum</i> infection during OVA sensitization on AAD were assessed and compared with uninfected and nonsensitized controls. Current, but not resolved, infection attenuated hallmark features of AAD: pulmonary eosinophil influx, T cell production of IL-5, mucus-secreting cell hyperplasia, and AHR. Current infection also induced robust OVA-driven neutrophilic inflammation and IFN-γ release from T cells. The phenotype of suppressed but persistent Th2 responses in association with enhanced neutrophilia is reminiscent of neutrophilic asthma. This phenotype was also characterized by increased pulmonary IL-12 and IL-17 expression and activation of APCs, as well as by reduced thymus- and activation-regulated chemokine. Inhibition of pulmonary neutrophil influx during infection blocked OVA-induced neutrophilic inflammation and T cell IFN-γ production and reversed the suppressive effects on mucus-secreting cell hyperplasia and AHR during AAD. These changes correlated with decreased IL-12 and IL-17 expression, increased thymus- and activation-regulated chemokine and altered APC activation. Blocking IFN-γ and IL-17 during OVA challenge had no effect. Thus, active chlamydial respiratory infection during sensitization enhances subsequent neutrophilic inflammation and Th1/Th17 responses during allergen exposure and may have a role in the pathogenesis of neutrophilic asthma.