T-bet deficiency facilitates airway colonization by Mycoplasma pulmonis in a murine model of asthma.

نویسندگان

  • Chandra Shekhar Bakshi
  • Meenakshi Malik
  • Pauline M Carrico
  • Timothy J Sellati
چکیده

Epidemiological and clinical evidence suggest a correlation between asthma and infection with atypical bacterial respiratory pathogens. However, the cellular and molecular underpinnings of this correlation remain unclear. Using the T-bet-deficient (T-bet(-/-)) murine model of asthma and the natural murine pathogen Mycoplasma pulmonis, we provide a mechanistic explanation for this correlation. In this study, we demonstrate the capacity of asthmatic airways to facilitate colonization by M. pulmonis and the capacity of M. pulmonis to exacerbate symptoms associated with acute and chronic asthma. This mutual synergism results from an inability of T-bet(-/-) mice to mount an effective immune defense against respiratory infection through release of IFN-gamma and the ability of M. pulmonis to trigger the production of Th2-type cytokines (e.g., IL-4 and IL-5), and Abs (e.g., IgG1, IgE, and IgA), eosinophilia, airway remodeling, and hyperresponsiveness; all pathophysiological hallmarks of asthma. The capacity of respiratory pathogens such as Mycoplasma spp. to dramatically augment the pathological changes associated with asthma likely explains their association with acute asthmatic episodes in juvenile patients and with adult chronic asthmatics, >50% of whom are found to be PCR positive for M. pneumoniae. In conclusion, our study demonstrates that in mice genetically predisposed to asthma, M. pulmonis infection elicits an inflammatory milieu in the lungs that skews the immune response toward the Th2-type, thus exacerbating the pathophysiological changes associated with asthma. For its part, airways exhibiting an asthmatic phenotype provide a fertile environment that promotes colonization by Mycoplasma spp. and one which is ill-equipped to kill and clear respiratory pathogens.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Tanshinone IIA attenuates ovalbumin-induced airway inflammation and hyperresponsiveness in a murine model of asthma

Objective(s): Tanshinone IIA (T. IIA), one of the most pharmacologically active components extracted from Salviae miltiorrhiza, has anti-inflammatory and antioxidant features. The aim of the present study is to investigate the benefit of T. IIA on asthma using a murine model of asthma induced by ovalbumin (OVA). Materials and Methods: Male BALB/c mice were used in the present study. The mice we...

متن کامل

Mycoplasma pulmonis inhibits electrogenic ion transport across murine tracheal epithelial cell monolayers.

Murine chronic respiratory disease is characterized by persistent colonization of tracheal and bronchial epithelial cell surfaces by Mycoplasma pulmonis, submucosal and intraluminal immune and inflammatory cells, and altered airway activity. To determine the direct effect of M. pulmonis upon transepithelial ion transport in the absence of immune and inflammatory cell responses, primary mouse tr...

متن کامل

Evaluation of Mycoplasma Muris and Pulmonis infections in Genital and Respiratory Tracts

Abstract Mycoplasma pulmonis and muris infections have been associated with several diseases in conventionally housed laboratory rat and mice colonies. In naturally infected of mycoplasma pulmonis in mice and rat colonies, the respiratory organ appears to be the favored site of colonization; so, it was not surprising to see that infection spread from the site of urogenital tract to the respirat...

متن کامل

Study of Chenopodium Album Allergenic Extract to Induce Allergic Asthma in Murine Model

Background: The incidence of allergic and asthmatic diseases has been continuously increased in both industrial and developing countries. Extracts from various known allergens are used for the diagnostic and therapeutic purposes. Objective: To investigate the effects of an extract prepared from Chenopodium album (Ch.A.) pollen to induce allergic asthma in BALB/C mice. Methods: BALB/C mice were ...

متن کامل

Ca2+-signaling in airway smooth muscle cells is altered in T-bet knock-out mice

BACKGROUND Airway smooth muscle cells (ASMC) play a key role in bronchial hyperresponsiveness (BHR). A major component of the signaling cascade leading to ASMC contraction is calcium. So far, agonist-induced Ca2+-signaling in asthma has been studied by comparing innate properties of inbred rat or mouse strains, or by using selected mediators known to be involved in asthma. T-bet knock-out (KO) ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of immunology

دوره 177 3  شماره 

صفحات  -

تاریخ انتشار 2006