Oxygen tensions play an important role in the outcome of infections. Oxygen is cidal or static for microorganisms that lack defenses against oxidants. Hyperoxia and hyperbaric oxygen exert antimicrobial effects by increasing the intracellular flux of reactive oxygen species. In bacteria, such species cause DNA strand breaks, degradation of RNA, inhibition of amino acid biosynthesis, and inactivation of membrane transport proteins. Oxygen tensions also affect the activity of antimicrobial agents. In general, hyperoxia potentiates while anaerobiosis decreases the activity of many antimicrobial drugs. With regard to host defenses, hyperoxia elevates oxygen tensions in infected tissues to levels that facilitate oxygen-dependent killing by leukocytes. Prolonged hyperoxia inhibits DNA synthesis in lymphocytes and impairs chemotactic activity, adherence, phagocytic capacity, and generation of the oxidative burst in polymorphonuclear leukocytes and macrophages.

Monokine induced by IFN-γ (Mig; CXC chemokine ligand 9) is an IFN-γ-inducible CXC chemokine that signals through the receptor CXCR3 and is known to function as a chemotactic factor for human T cells, particularly following T cell activation. The mig gene can be induced in multiple cell types and organs, and Mig has been shown to contribute to T cell infiltration into immune/inflammatory reactions in peripheral tissues in mice. We have investigated the expression and activities of Mig and CXCR3 in mouse cells and the role of Mig in models of host defense in mice. Murine (Mu)Mig functioned as a chemotactic factor for resting memory and activated T cells, both CD4+ and CD8+, and responsiveness to MuMig correlated with surface expression of MuCXCR3. Using mig−/− mice, we found that MuMig was not necessary for survival after infections with a number of intracellular pathogens. Surprisingly, however, we found that mig−/− mice showed reductions of 50–75% in Abs produced against the intracellular bacterium Francisella tularensis live vaccine strain. Furthermore, we found that MuMig induced both calcium signals and chemotaxis in activated B cells, and that B cell activation induced expression of MuCXCR3. In addition, IFN-γ induced the expression of mumig in APCs, including CD8α+ and CD8α− dendritic cells. Together, our data suggest that Mig and CXCR3 may be important not only to recruit T cells to peripheral inflammatory sites, but also in some cases to maximize interactions among activated T cells, B cells, and dendritic cells within lymphoid organs to provide optimal humoral responses to pathogens.

Hydrocephalus can be associated with increased morbidity and mortality in cryptococcal meningitis if left untreated. Both ventriculoperitoneal and ventriculoatrial shunting have been used in persons with cryptococcosis complicated by hydrocephalus, but the indications for and complications, success, and timing of these interventions are not well known. To this end, we reviewed the clinical courses of 10 non-human immunodeficiency virus-infected patients with hydrocephalus secondary to cryptococcal meningitis who underwent shunting procedures. Nine of 10 patients who underwent shunting had noticeable improvement in dementia and gait. Two patients required late revision of their shunts. Shunt placement in eight patients with acute infection did not disseminate cryptococcal infection into the peritoneum or bloodstream, nor did shunting provide a nidus from which Cryptococcus organisms proved difficult to eradicate. Shunting procedures are a safe and effective therapy for hydrocephalus in patients with cryptococcal meningitis and need not be delayed until patients are mycologically cured.