title: The integrins Mac-1 and alpha4beta1 perform crucial roles in neutrophil and T cell recruitment to lungs during Streptococcus pneumoniae infection.
abstract: Neutrophils and T cells play an important role in host protection against pulmonary infection caused by Streptococcus pneumoniae. However, the role of the integrins in recruitment of these cells to infected lungs is not well understood. In this study we used the twin approaches of mAb blockade and gene-deficient mice to investigate the relative impact of specific integrins on cellular recruitment and bacterial loads following pneumococcal infection. We find that both Mac-1 (CD11b/CD18) and α(4)β(1) (CD49d/CD29) integrins, but surprisingly not LFA-1 (CD11a/CD18), contribute to two aspects of the response. In terms of recruitment from the circulation into lungs, neutrophils depend on Mac-1 and α(4)β(1), whereas the T cells are entirely dependent on α(4)β(1). Second, immunohistochemistry results indicate that adhesion also plays a role within infected lung tissue itself. There is widespread expression of ICAM-1 within lung tissue. Use of ICAM-1(-/-) mice revealed that neutrophils make use of this Mac-1 ligand, not for lung entry or for migration within lung tissue, but for combating the pneumococcal infection. In contrast to ICAM-1, there is restricted and constitutive expression of the α(4)β(1) ligand, VCAM-1, on the bronchioles, allowing direct access of the leukocytes to the airways via this integrin at an early stage of pneumococcal infection. Therefore, integrins Mac-1 and α(4)β(1) have a pivotal role in prevention of pneumococcal outgrowth during disease both in regulating neutrophil and T cell recruitment into infected lungs and by influencing their behavior within the lung tissue itself.
authors: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom. ak13@le.ac.uk
authors: Aras
authors: A
authors: Kadioglu
authors: Katia
authors: K
authors: De Filippo
authors: Mathieu
authors: M
authors: Bangert
authors: Vitor E
authors: VE
authors: Fernandes
authors: Luke
authors: L
authors: Richards
authors: Kristian
authors: K
authors: Jones
authors: Peter W
authors: PW
authors: Andrew
authors: Nancy
authors: N
authors: Hogg
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000911:Antibodies, Monoclonal; D002465:Cell Movement; D039041:Integrin alpha4beta1 / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1