Function of myosin If in neutrophil and memory T cell responses

To investigate the mechanisms underlying enhanced protection provided by memory T cell responses, we screened genes specifically expressed in CD4 memory T cells comparing them with CD4 naive and effector T cells, by using subtraction and microarray analysis. Using the criteria of degree of increase in expression, pattern of expression and comparison of different screening methods, led us to Myosin If, which is highly expressed in both CD4 and CD8 memory T cells. To determine the role of myosin If in memory T cells, T cell-specific conditional knockout mice were generated. Enhanced protection, CD8 memory T cell generation and migration into non-lymphoid tissues are not impaired in the absence of myosin If, as judge by in vivo infection models. Myosin If is also enriched in other cells in the immune system and particularly neutrophils show the exclusive expression of myosin If without a significant expression of other amoeboid myosin I. To investigate the function of vertebrate myosin If, knockout mice were generated and analyzed. While IgG-mediated phagocytosis, fluidphase endocytosis, production of reactive oxygen species are not impaired, we observed abnormally increased adhesion, increased actin polymerization and impaired migration in myosin If-deficient neutrophils. To further determine physiological importance of this phenotype, immunity against Listeria monocytogenes was tested in vivo in the absence of myosin If. The ability to control bacteria in early phase of the infections, is impaired in mice lacking myosin If and the development of neutrophil-dependent cellular responses is impaired in myosin If-knockout mice. Finally, adoptive transfer of neutrophils into the recipient mice during Listeria infection proved that myosin If-deficient neutrophils have a cell-autonomous defect in recruitment into the infection site in vivo.