Characterization and Function of the Inflammatory Response to Infection by a Gastrointestinal Nematode Parasite: New Insights into Protective Th2 Responses
Abstract
Effective immune responses to infectious diseases involve appropriate primary and secondary reactions mediating host protection. Th2 effector mechanisms leading to host-protection remain elusive. Using an infectious model employing a nematode parasite, Heligmosomoides polygyrus, we characterized the immune cell infiltrate surrounding invasive larval parasites in the small intestinal muscosa and submucosa (host:parasite interface) during early stages of a secondary infection. A primary is chronic, with established adult parasites detectable up to four months post infection, where as the parasites are naturally cleared from the intestinal lumen by 14 days follow challenge. This distinction between primary and secondary H. polygyrus infections allows a clear readout of protective immunity, making this infectious model useful for examining protective secondary Th2 responses. A distinct and highly reproducible leukocyte architecture developed by the fourth day post challenge, which included CD4+ T cells surrounding the parasite. Additionally, laser capture microdissected (LCM) samples from the host:parasite interface featured upregulated Th2 cytokine mRNAs relative to untreated intestinal tissue. This localized inflammatory response differed during primary infection, as CD4+ T cells did not infiltrate the host:parasite interface, and there were no increases in cytokine expression. These findings were extended to show that the peripheral inflammation during the memory Th2 response at the host:parasite interface is essential for host-protection leading to worm expulsion. Memory CD4+ T cells that express Th2 cytokines rapidly accumulate around the invading parasite and induce the alternative activation of macrophages. Alternatively activated macrophages metabolize the amino acid, arginine, by the enzyme arginase-1. Our findings demonstrate that macrophages and arginase contribute to the natural clearance of a secondary H. polygyrus infection.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2006
- Accession Number
- ADA459045
Entities
People
- Robert M. Anthony
Organizations
- Uniformed Services University of the Health Sciences