Integrin alpha-1 deficiency does not affect resistance to pulmonary Mycobacterium tuberculosis infection in mice but leads to necrosis within granulomatous lesions (97.12)

Abstract

Abstract The hallmark of Mycobacterium tuberculosis infection is the granuloma, a highly dynamic immune structure that ‘walls off’ the bacilli during chronic infection. Here, we examined if α1β1 integrin is required in the development and maintenance of the granulomatous structure during infection using an α1-integrin knockout mouse (α1-null). The α1β1 integrin is expressed on activated macrophages and T cells, and interacts with collagen molecules in the extracellular matrix (ECM). To determine if the α1-integrin molecule is necessary for trafficking of activated T cell within the lungs, cells from the lungs of infected α1-null mice were stained for CD4, CD44 and CD62L. The numbers of activated and IFNγ-producing CD4-positive T cells were increased in the α1-null strain during chronic infection. While there were no differences in bacterial load between the α1-null and wild type mice, histology revealed striking differences in granuloma formation and structure. MMP-9 and TNFα were decreased in the α1-null mice and alveolar septae were distinct and markedly thickened. By day 180, there were regions of necrosis within the granulomas, characterized by cellular and nuclear debris. These results reveal that while the α1β1 integrin is not a factor required for resistance to M. tuberculosis, it does play a role in granuloma formation and integrity of the structure. Funding: NIH AI52040 and Colorado State University CRC