The LFA-1 adhesion molecule is required for protective immunity during pulmonary Mycobacterium tuberculosis infection.
Host immunity to Mycobacterium tuberculosis is mediated by T cells that recognize and activate infected macrophages to control intracellular bacterial replication. The early appearance of T cells in the lungs of infected mice correlates with greater resistance to infection. However, it is unknown whether the trafficking of T cells to the lung following infection is dependent upon the expression of certain adhesion molecules. To address this question, we infected knockout (KO) mice that have defective expression of CD11a, CD11b, CD18, CD62, CD103, or beta7. We found that the integrins CD11a and CD18 are absolutely required for host resistance following infection with aerosolized M. tuberculosis. Although Ag-specific T cells are generated following infection of CD11a KO mice, T cell priming is delayed, T cell trafficking to the lung is impaired, and fewer ESAT6-specific CD4+ T cells are found in the lungs of CD11a KO mice compared with control mice. Thus, LFA-1 (CD11a/CD18) plays an essential role in immunity to M. tuberculosis infection.
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Shamik
S
Ghosh
Alissa A
AA
Chackerian
Christina M
CM
Parker
Christie M
CM
Ballantyne
Samuel M
SM
Behar
D000818:Animals; D040881:CD11a Antigen / Q000235:genetics / Q000378:metabolism; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D005260:Female; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
D040881:CD11a Antigen; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1