Protein calorie malnutrition and immunological memory

Protein calorie malnutrition (PCM) occurs when there is a deficiency in the diet of either protein and/or calories. PCM is associated with increased rate and duration of infections. We first established a mouse model that showed the effects of PCM in adult mice and then used these mice to understand how PCM increases susceptibility to infections.; Adult mice were fed a low protein (LP) diet for 8 weeks to induce PCM. These mice showed the effects of severe malnutrition such as weight loss, decreased primary and secondary lymphoid organ weights and cell numbers, and disrupted frequencies of lymphocyte subsets within the thymus.; Since PCM has been shown to increase the incidence and severity of infection, we hypothesized that reduction in the expansion of viral-specific cells and the microenvironment of the host leads to increased incidence and severity of infections. We tested this hypothesis using a mouse model of lymphocytic choriomeningitis virus (LCMV) infection. Our data demonstrated that during PCM, there is diminished expansion of primary viral-specific CD8 T cells. Additionally, in naive LP diet fed mice given a LCMV infection, there was an inability to clear virus. Furthermore, our data showed that the diminished primary CD8 T cell response during PCM may in part be due to low numbers of viral-specific CD8 T cells and an altered microenvironment during PCM and is not due to intrinsic changes in CD8 T cells.; Memory cells are an important component of long-term protective immunity and are maintained through homeostatic proliferation. Since PCM suppresses the generation of memory CD8 T cells, we hypothesized that PCM leads to reduced homeostatic proliferation of memory CD8 T cells and reduced generation of secondary viral-specific cells upon re-infection. Despite being in a lymphopenic environment, viral-specific memory CD8 T cells in mice fed the LP diet showed a marked reduction in homeostatic proliferation when compared to mice fed the AP diet. Also, viral-specific memory CD8 T cells in mice fed the LP diet did not expand as viral-specific memory CD8 T cells in mice fed the AP diet and mice fed the LP diet had more virus in the tissues compared to mice fed the AP diet upon re-infection.; Collectively, these studies have extended our mechanistic understanding of the effects of PCM on immune function and infection.