The last century is notable for the remarkable successes
made in the area of antibiotic and vaccine development
against infectious agents. However, as we enter the
beginning of the next century, the singular most common
cause of morbidity and mortality in man and animals
continues to be infectious diseases. With the anticipated
growth in the aged and immunocompromised populations
in our midst, there is an acute need for the development
of alternate approaches to curb microbial infections
and their harmful sequellae.
This laboratory is interested in studying the mechanisms
and consequences of the molecular interactions occurring
between pathogenic bacteria and inflammatory cells.
We believe that there is a significant amount of crosstalk
occurring between bacteria and immune cells of the
host and the outcome dictates the pathology associated
with bacterial infection as well as the survival of
the pathogen in the host. There are two distinct research
interests involving host-pathogen crosstalk. The first
is centered around the interactions of mast cells
with microbial pathogens and the role mast cells play
in modulating the host’s immune system following
bacterial infections. We have discovered that mast
cells play a critical and previously unrecognized
role in modulating the innate and adaptive immune
responses to pathogens. In the abscence of mast cells
recruitment of neutrophils to sites of infection and
the swelling of draining lymph nodes following infection
fails to occur. The second focuses on elucidating
the molecular basis for how pathogens gain access
into host cells without triggering their intrinsic
microbicidal activities. It is now clear that microbial
persistence in the host is achieved through seeking
refuge within various host cells. A recently discovered
route of microbial invasion appears to involve distinct
host cell surface entities called lipid rafts (a subpopulation
of which are known as caveolae).
Our work should have important implications in the
understanding of hitherto poorly understood aspects
of cell biology, the innate immune system and bacterial
pathogenesis. These studies should facilitate the
design of novel strategies that can selectively potentiate
the microbicidal activity of inflammatory cells without
increasing the harmful effects of inflammation.
