INFECTIONS OF CATTLE BY GASTROINTESTINAL (GI) NEMATODE PARASITES CAN COST MORE THAN $2 BILLION PER YEAR IN THE UNITED STATES ALONE. OSTERTAGIOSIS, CAUSED BY PARASITE O. OSTERTAGI, ACCOUNTS FOR A SIGNIFICANT PORTION OF THE ECONOMIC LOSSES DUE TO ALL GI NEMATODES IN LIVESTOCK PRODUCTION. TREATMENTS ARE CURRENTLY LIMITED TO ANTHELMINTICS; HOWEVER, ANTHELMINTIC DRUG RESISTANCE IN CATTLE PARASITES IS ON THE RISE BOTH IN THE US AND ACROSS THE GLOBE. PREVAILING FARMING PRACTICES INCLUDING OVERUSE AND MISUSE OF DRUGS COUPLED WITH A SURGE IN INTENSIFIED FARMING HAVE EXACERBATED THIS PROBLEM. CURRENTLY, THERE IS NO VACCINE FOR BOVINE OSTERTAGIOSIS.FUNCTIONAL ANTIGEN PRESENTING CELLS (APCS) ARE ESSENTIAL IN ORCHESTRATING IMMUNE DEFENSES AGAINST PATHOGEN INVASION. TRADITIONALLY, NEUTROPHILS ARE CONSIDERED ONE OF THE FIRST-RESPONDERS OF THE IMMUNE SYSTEM, BUT THEIR FUNCTIONS AS APCS ARE UNKNOWN IN CATTLE. IN THIS PROJECT, WE WILL FIRST COMPARE THE ANTIGEN-PRESENTATION FUNCTION OF BOVINE NEUTROPHILS WITH CLASSICAL APCS, SUCH AS DENDRITIC CELLS. WE WILL THEN EXAMINE THE MECHANISMS BY WHICH PARASITE O. OSTERTAGI MAY CO-OPT THESE FUNCTIONS TO SUPPRESS THE INDUCTION OF SPECIFIC IMMUNE RESPONSES AND THEREBY FACILITATE THEIR SURVIVAL IN THEIR HOST, OSTERTAGIA-INFECTED CATTLE. FINALLY, WE WILL IDENTIFY CRITICAL MOLECULAR TARGETS ASSOCIATED WITH STIMULATORY OR INHIBITORY FUNCTIONS RELATED TO ANTIGEN PRESENTATION BY NEUTROPHILS, IN HOPES OF UTILIZING THIS KNOWLEDGE TO IMPROVE IMMUNE INTERVENTIONS IN BOVINE DISEASE. THERE ARE THREE AIMS IN THIS PROJECT:AIM 1: DELINEATE REGULATORY FUNCTIONS OF MHC II+ NEUTROPHILSAIM 2: DEFINE MODULATION OF MHC II+ NEUTROPHILS BY O. OSTERTAGIAIM 3: EXAMINE MOLECULAR MECHANISMS OF ANTIGEN PRESENTATION BY MHC II+ NEUTROPHILS