Impairment of protective immunity to intestinal helminthiases
Modulation of immune responses to helminth infections by concurrent protozoan pathogens has been shown in many human epidemiological studies. We established a murine model of coinfection with an intracellular apicomplexan, E. falcifomis, and the gastrointestinal helminth N. brasiliensis. The role of Stat 6 (signal transducers and activators of transcription) and Stat4 in the recruitment of eosinophils during coinfection with both parasites was investigated. Results of this study demonstrated that eosinophil responses occur in a Stat6-dependent manner in mice infected with the intestinal nematode, N. brasiliensis. Prominent blood eosinophilia was induced in wild type Balb/c mice, whereas in Stat6 -/- mice eosinophil responses were considerably reduced. Reversal of blood eosinophil profile was noted in N. brasiliensis-infected Stat4-deficient mice. Oral infection with E. falciformis of Stat6-/-, Stat4-/-, and wild type mice following N. brasiliensis infection inhibited the development of TH2-associated peripheral eosinophilia. Mortality of coinfected Stat6-deficient mice was higher than that of Stat4 and wild type mice. Splenocytes of Stat6 -/- mice produced lower levels of interferon-gamma during concurrent infection with E. falciformis than Stat6-deficient mice infected with N. brasiliensis alone; suggesting alternative mechanisms of cytokine production. These results demonstrate that a concurrent infection with the protozoan, E. falciformis strongly modulates multiple aspects of an established TH2 immunity to N. brasiliensis and consequently impairs the development of protective immunity to this intestinal helminth infection. ^
Al-Dahwi, Zaineb, "Impairment of protective immunity to intestinal helminthiases" (2007). ETD Collection for University of Texas, El Paso. AAI3291007.