Terry W. Wright, Ph.D.

1) Pneumocystis carinii biology
2) Pathogenesis of lung injury during Pneumocystis carinii pneumonia.

The rapid clearance of bacterial and fungal pathogens is essential to preserve the delicate structure and critical function of the lung. The opportunistic pathogen, Pneumocystis carinii, colonizes the alveolar epithelium of patients suffering from a variety of immunodeficiencies, including AIDS. Dr. Wright's laboratory uses an immunologically-reconstituted scid mouse model of Pneumocystis carinii pneumonia (PCP) to study the host response to infection. Scid mice lack functional lymphocytes and therefore develop active P. carinii infections. However, the adoptive transfer of congenic spleen cells, including CD4+ T lymphocytes, to P. carinii-infected scid mice results in inflammatory cell recruitment to sites of infection and organism clearance. They are now examining the earliest molecular signals (including cytokine and chemokine expression) produced at epithelial sites of P. carinii colonization, to determine which cell types and which soluble mediators are involved in targeting inflammatory cell recruitment. These studies will not only further our understanding of PCP, but may also provide insight into general mechanisms of lung defense.

In addition, they are examining the role of pulmonary inflammation in the pathology of PCP. As stated above, an intense CD4+ T lymphocyte-dependent inflammatory response is mounted at sites of infection in reconstituted scid mice. In many cases this inflammatory response is productive, and serves to resolve the infection. However, under certain circumstances the inflammatory response may actually contribute to the pulmonary injury and respiratory impairment observed in P. carinii pneumonia. They have begun studies using physiological and molecular measurements of lung injury to assess the in vivo role of P. carinii driven inflammation in PCP. They also plan to test specific anti-inflammatory agents to manipulate various aspects of the inflammatory response to determine the effect on lung injury. These studies will help define the role of inflammation in PCP, and further our understanding of pulmonary immunology.

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