** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** INFLAMMATORY STIMULI SUCH AS INFECTIOUS DISEASE INCUR SIGNIFICANT COSTS TO SWINE PRODUCTION. ONE IMPORTANT CONSEQUENCE OF INFLAMMATION IS THE REDIRECTION OF METABOLIC RESOURCES AWAY FROM WEIGHT GAIN RESULTING IN SIGNIFICANT PRODUCTION LOSSES. CD163 AN IMPORTANT RECEPTOR FOR PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME VIRUS (PRRSV) ALSO PARTICIPATES IN THE REGULATION OF INFLAMMATION. IN PRELIMINARY WORK WE SHOWED THAT CD163 KNOCKOUT (KO) PIGS INFECTED WITH A PORCINE CIRCOVIRUS TYPE 2D (PCV2D) ANOTHER IMPORTANT PIG PATHOGEN SHOWED RESISTANCE TO INFECTION. WE PROPOSE THAT THE ABSENCE OF CD163 PROTECTS PIGS BY DOWNREGULATING PATHOGEN-MEDIATED INFLAMMATORY RESPONSES. THE PROPOSED RESEARCH PROJECT TESTS THIS HYPOTHESIS BY MEASURING INFLAMMATORY RESPONSES IN CD163 WILD-TYPE (WT) AND KO PIGS DURING INFECTION WITH PCV2D. THE EXPERIMENTAL APPROACH IS THE APPLICATION OF NOVEL GENE PROFILING AND PATHWAY ANALYSIS METHODS TO MAP INFLAMMATORY RESPONSES IN INDIVIDUAL IMMUNE CELL POPULATIONS. OBJECTIVE 1 IS TO COMPARE GENE PROFILES IN MACROPHAGES FROM CD163 WT AND KO PIGS. MACROPHAGES ARE CHOSEN FOR STUDY BECAUSE THEY EXPRESS CD163 AND AS A RESULT ARE KEY MEDIATORS IN THE INITIATION AND REGULATION OF INFLAMMATION. THE METHODS AND RESULTS FROM OBJECTIVE 1 WILL BE APPLIED TO SUBSEQUENT OBJECTIVES. OBJECTIVE 2 IS TO EVALUATE GENE EXPRESSION IN CD163 WT AND KO MACROPHAGES DURING INFECTION WITH PCV2D AND OTHER MACROPHAGE-TROPIC VIRUSES. GENE PROFILES WILL BE CONSTRUCTED IN MACROPHAGES DURING INFECTION WITH PCV2D AND A VARIETY OF IMPORTANT PIG CORONAVIRUSES. THE RESULTS WILL BE USED TO UNDERSTAND THE EFFECT OF PCV2D INFECTION ON THE INFLAMMATORY RESPONSE OF MACROPHAGES AND TO DETERMINE IF THE RESPONSE IS A GENERAL PROPERTY THAT CAN BE APPLIED TO OTHER PATHOGENS. OBJECTIVE 3 IS TO CONSTRUCT GENE PROFILES OF IMMUNE CELL POPULATIONS IN WT AND KO PIGS DURING PCV2D INFECTION. GENE PROFILES AND INFLAMMATORY RESPONSE PATHWAYS WILL BE MAPPED IN IMPORTANT CELL POPULATIONS SORTED FROM THE BLOOD OF PIGS. IMPORTANT IMMUNE CELL POPULATIONS INVESTIGATED INCLUDE MONOCYTES B CELLS AND T CELLS. BLOCKING CD163 FUNCTION MAY PROTECT PIGS FROM INFLAMMATION CAUSED BY NON-INFECTIOUS STRESSORS SUCH AS WEANING ENVIRONMENTAL CHANGES AND INFLAMMATORY CYTOKINES PRODUCED IN RESPONSE TO FAST-GROWTH DIETS. ALTOGETHER THE REGULATION OF CD163 FUNCTION WOULD RESULT IN A PIG THAT IS BETTER ADAPTED TO THE MODERN PRODUCTION SYSTEM.