CD44 Deficiency Is Associated with Increased Bacterial Clearance but Enhanced Lung Inflammation During Gram-Negative Pneumonia

Klebsiella pneumoniae is a frequently isolated causative pathogen in respiratory tract infections. CD44 is a transmembrane adhesion molecule that has been implicated in several immunological processes. To determine the role of CD44 during Klebsiella pneumonia, we intranasally infected wild-type and CD44 knockout (KO) mice with 102 to 104 colony-forming units of K. pneumoniae or administered Klebsiella lipopolysaccharide. During lethal infection, CD44 deficiency was associated with reduced bacterial growth and dissemination accompanied by enhanced pulmonary inflammation. After infection with lower Klebsiella doses, CD44 KO mice but not wild-type mice demonstrated mortality. After infection with even lower bacterial doses, which were cleared by most mice of both strains, CD44 KO mice displayed enhanced lung inflammation 4 and 10 days postinfection, indicating that CD44 is important for the resolution of pulmonary inflammation after nonlethal pneumonia. In accordance, CD44 KO mice showed a diminished resolution of lung inflammation 4 days after intrapulmonary delivery of lipopolysaccharide. CD44 deficiency was associated with the accumulation of hyaluronan together with reduced gene expression levels of the negative regulators of Toll-like receptor signaling, interleukin-1R-associated kinase M, A20, and suppressor of cytokine signaling 3. In conclusion, the absence of CD44 affects various components and phases of the host response during Klebsiella pneumonia, reducing bacterial outgrowth and dissemination and enhancing pulmonary pathology during lethal infection, and diminishing the resolution of lung inflammation during sublethal infection

Food-web regulation by a planktivore: exploring the generality of the trophic cascade hypothesis

The trophic cascade hypothesis currently being tested in north temperate systems may not apply to open-water communities in lower latitude U.S. reservoirs. These reservoir communities differ dramatically from northern lakes in that an open-water omnivore, gizzard shad (Dorosoma cepedianum), often occurs in abundance. Neither controlled by fish predators (owing to high fecundity and low vulnerability) nor by their zooplankton prey (following the midsummer zooplankton decline, gizzard shad consume detritus and phytoplankton), gizzard shad regulate community composition rather than being regulated by top-down or bottom-up forces. In experiments across a range of spatial scales (enclosures, 1-9 m2; ponds, 4-5 ha; and reservoirs, 50-100 ha), we evaluated the generality of the trophic cascade hypothesis by assessing its conceptual strength in reservoir food webs. We reviewed the role of gizzard shad in controlling zooplankton populations and hence recruitment of bluegill, Lepomis macrochirus (via exploitative competition for zooplankton), and largemouth bass, Micropterus salmoides (by reducing their bluegill prey). Reservoir fish communities, owing to the presence of gizzard shad, appear to be regulated more by complex weblike interactions among species than by the more chainlike interactions characteristic of the trophic cascade.Funding for this project was provided by National Science Foundation (NSF) grants DEB9107173 and DEB9407859 to R.A.S. and NSF grants DEB9108986 and DEB9410323 to D.R.D