Lack of alpha-1 integrin alters lesion morphology during pulmonary Mycobacterium tuberculosis infection.
The hallmark of Mycobacterium tuberculosis infection is the granuloma, a highly dynamic immune structure that contains the bacilli during chronic infection. Here, we examined if alpha1beta1 integrin is required in the development and maintenance of the granulomatous structure during pulmonary infection using the alpha1 integrin knockout (alpha1-null) mouse. The alpha1beta1 integrin is expressed on activated macrophages and T cells, and interacts with collagen molecules in the extracellular matrix (ECM), and thus may play a role in the granulomatous process. Following pulmonary infection with virulent M. tuberculosis, lungs of alpha1-null infected mice had striking differences in granuloma structure, as well as distinct and markedly thickened alveolar septae. By day 180, there were regions of cell death within granulomatous lesions, characterized by cellular debris in these mice. To determine if this molecule was necessary for T cell trafficking within the lungs, the expression of CD4, CD44 and CD62L was monitored. The number of activated and IFN-gamma-producing CD4+ T cells increased in the lungs of alpha1-null mice during the chronic phase of infection, although they had decreased concentrations of TNF-alpha and MMP-9. These results suggest that while alpha1beta1 integrin is not required for trafficking or maintenance of T cells in M. tuberculosis infected lungs, it does play a role in granuloma structure and integrity during the chronic phase of infection.
Taylor
Jennifer L
JL
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA. Jennifer.L.Taylor@Colostate.edu
Bielefeldt-Ohmann
Helle
H
Pozzi
Ambra
A
Izzo
Angelo A
AA
D000818:Animals; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006099:Granuloma / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D039041:Integrin alpha4beta1 / Q000172:deficiency* / Q000276:immunology; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
D039041:Integrin alpha4beta1