Aged mice display an altered pulmonary host response to Francisella tularensis live vaccine strain (LVS) infections.

Aging is a complex phenomenon that has been shown to affect many organ systems including the innate and adaptive immune systems. The current study was designed to examine the potential effect of immunosenescence on the pulmonary immune response using a Francisella tularensis live vaccine strain (LVS) inhalation infection model. F. tularensis is a Gram-negative intracellular pathogen that can cause a severe pneumonia. In this study both young (8-12 week old) and aged (20-24 month old) mice were infected intranasally with LVS. Lung tissues from young and aged mice were used to assess pathology, recruitment of immune cell types and cytokine expression levels at various times post infection. Bacterial burdens were also assessed. Interestingly, the lungs of aged animals harbored fewer organisms at early time points of infection (day 1, day 3) compared with their younger counterparts. In addition, only aged animals displayed small perivascular aggregates at these early time points that appeared mostly mononuclear in nature. However, the kinetics of infiltrating polymorphonuclear neutrophils (PMNs) and increased cytokine levels measured in the bronchial alveolar lavage fluid (BALF) were delayed in infected aged animals relative to young infected animals with neutrophils appearing at day 5 post infection (PI) in the aged animals as opposed to day 3 PI in the young infected animals. Also evident were alterations in the ratios of mononuclear to PMNs at distinct post infection times. The above evidence indicates that aged mice elicit an altered immune response in the lung to respiratory F. tularensis LVS infections compared to their younger counterparts.

Comparison of V kappa gene family expression in adult and fetal B cells.

The functional B cell repertoires from adult and fetal mice were compared by examining V kappa gene family expression in individual cells. In addition, because little is known about the relative use of the various V kappa gene families in an immune response, adult B cells from several different strains of mice were analyzed. This was accomplished by stimulating B cells with the polyclonal activator, LPS. Activated cells were then analyzed for V kappa gene family expression at the single cell level by in situ hybridization using radiolabeled V kappa gene probes. It was found that all V kappa gene families tested were represented in the LPS-induced adult repertoire with V kappa 1, V kappa 4,5 and V kappa 19 being expressed to the largest degree in all strains tested. The LPS-induced adult V kappa gene family repertoire was then compared to the fetal repertoire and some differences were observed. In particular, a lower proportion of fetal B cells expressed V kappa 1 and a higher proportion of fetal B cells expressed V kappa 4,5 and V kappa 10. Importantly, compared with the adult response there was no evidence in the fetal response for an increased expression of V kappa 21, the family that maps closest to J kappa,C kappa. This is in contrast to what has been shown previously with H chain V region exons in which there was a clear preference for the VH gene families that mapped closest to DH.