transforming-growth-factor-beta and Pneumonia--Pneumococcal

Immune response and restructuring of tissue during organ fibrosis mutually influence each other. It has become evident that the immunomodulatory properties of lining cells of the lung, such as bronchial or alveolar epithelial cells or pulmonary endothelial cells exert a major influence on the acute and chronic activation of the immune system. On the other hand, recent data obtained under in vivo conditions, suggest that the process of mesenchymal organ remodelling during inflammation not only causes organ fibrosis, but may actually perpetuate the process of chronic pulmonary inflammation due to its immunosuppressive effects. In this short review, two examples for this reciprocal influence are discussed.

Topics: Adjuvants, Immunologic; Animals; Humans; Immune Tolerance; Immunity, Cellular; Pneumonia, Pneumococcal; Pulmonary Fibrosis; Transforming Growth Factor beta

Allergic asthma (AA) is characterized as a Th2-biased airway inflammation that can develop lung inflammation and remodeling of the respiratory tract.

Topics: Animals; Asthma; Cells, Cultured; Disease Models, Animal; Disease Resistance; Goblet Cells; Humans; Hyperplasia; Hypersensitivity; Interleukin-6; Mice; Mice, Knockout; Pneumonia; Pneumonia, Pneumococcal; Respiratory Mucosa; RNA, Small Interfering; Signal Transduction; Streptococcus pneumoniae; Tight Junctions; Transforming Growth Factor beta

Streptococcus pneumoniae is an important human pathogen responsible for a spectrum of diseases including pneumonia. Immunological and pro-inflammatory processes induced in the lung during pneumococcal infection are well documented, but little is known about the role played by immunoregulatory cells and cytokines in the control of such responses. We demonstrate considerable differences in the immunomodulatory cytokine transforming growth factor (TGF)-β between the pneumococcal pneumonia resistant BALB/c and susceptible CBA/Ca mouse strains. Immunohistochemistry and flow cytometry reveal higher levels of TGF-β protein in BALB/c lungs during pneumococcal pneumonia that correlates with a rapid rise in lung Foxp3(+)Helios(+) T regulatory cells. These cells have protective functions during pneumococcal pneumonia, because blocking their induction with an inhibitor of TGF-β impairs BALB/c resistance to infection and aids bacterial dissemination from lungs. Conversely, adoptive transfer of T regulatory cells to CBA/Ca mice, prior to infection, prolongs survival and decreases bacterial dissemination from lungs to blood. Importantly, strong T regulatory cell responses also correlate with disease-resistance in outbred MF1 mice, confirming the importance of immunoregulatory cells in controlling protective responses to the pneumococcus. This study provides exciting new evidence for the importance of immunomodulation during pulmonary pneumococcal infection and suggests that TGF-β signalling is a potential target for immunotherapy or drug design.

Topics: Animals; Disease Susceptibility; DNA-Binding Proteins; Drug Delivery Systems; Female; Forkhead Transcription Factors; Mice; Mice, Inbred BALB C; Pneumonia, Pneumococcal; Signal Transduction; Species Specificity; Streptococcus pneumoniae; T-Lymphocytes, Regulatory; Transcription Factors; Transforming Growth Factor beta

We studied cytokine mRNA expression in Streptococcus pneumoniae carriage, pneumonia, and sepsis in 3-week-old, inbred C57BL/6 and BALB/c mice. Mice were inoculated intranasally with S. pneumoniae serotype 6B, 14, or 3. Survival, bacterial load in the nasopharynx (NP) and lungs, and mRNA levels of tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, interleukin (IL)-10, and IL-12 in the spleen were analyzed. No baseline mRNA expression levels were found, except for TNF-alpha in C57BL/6 mice. Serotype 6B caused NP colonization only, a significant (P<.05) increase in the levels of TNF-alpha, and induction of TGF-beta and IL-12 mRNA. Serotype 14 caused NP and nonlethal lung colonization and induction of TGF-beta, IL-10, and IL-12. Serotype 3 caused NP colonization, pneumonia, 35% mortality, and no alteration in the mRNA expression of tested cytokines. Although activation of the immune system culminated in nonlethal disease, evasion of the immune system was associated with detrimental disease.

Topics: Animals; Bacteremia; Carrier State; Cytokines; Interleukin-12; Lung; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nasopharynx; Pneumonia, Pneumococcal; RNA, Messenger; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha