Alternative-to-antibiotics strategies to enhance disease resistance against necrotic enteritis

Hyun. S. Lillehoj 한국가금학회 2012 한국가금학회 심포지움 Vol.2012 No.5

Development of antibiotics free alternative strategies to enhance gut immunity and to reduce harmful inflammatory responses due to necrotic enteritis. Hyun Lillehoj. Animal and Natural Resources Institute. United States Department of Agriculture. Agricultural Research Service. Beltsville, MD. USA. In the United States, necrotic enteritis(NE) is among the most important infectious diseases in poultry. Recently, NE has reemerged as a significant problem as a result of restricted use of in-feed antibiotics, high-density housing conditions, and the reuse of litter. Thus, there is an urgent need to develop rational and alternative management strategies not only to control but also to prevent NE. Better understanding of host-pathogen interaction in NE will be required to realize these goals. Our laboratory recently developed a NE disease model using dual challenge of E.maxima and C.perfringens. Using this NE model, we are currently developing various drug-free alternative strategies to enhance gut immunity and to reduce gut damage caused by NE-induced inflammatory response. This presentation will highlight some of the recent findings from my laboratory.

High-throughput Gene Expression Analysis to Investigate Host-pathogen Interaction in Avian Coccidiosis

Lillehoj Hyun, S. The Korean Society of Poultry Science 2007 韓國家禽學會誌 Vol.34 No.1

Poultry products including meat and eggs constitute a major protein source in the American diet and disease-causing pathogens represent major challenges to the poultry industry. More than 95% of pathogens enter the host through the mucosal surfaces of the respiratory, digestive and reproductive tracts and over the past few decades, the two main mechanisms used to control diseases have been the use of vaccines and antibiotics. However, in the poultry industry, there are mounting concerns over the ability of current vaccines to adequately protect against emerging hyper-virulent strains of pathogens and a lack of suitable, cost effective adjuvants. Thorough investigation of the immunogenetic responses involved in host-pathogen interactions will lead to the development of new and effective strategies for improving poultry health, food safety and the economic viability of the US poultry industry. In this paper, I describe the development of immunogenomic and proteomic tools to fundamentally determine and characterize the immunological mechanisms of the avian host to economically significant mucosal pathogens such as Eimeria. Recent completion of poultry genome sequencing and the development of several tissue-specific cDNA libraries in chickens are facilitating the rapid application of functional immunogenomics in the poultry disease research. Furthermore, research involving functional genomics, immunology and bioinformatics is providing novel insights into the processes of disease and immunity to microbial pathogens at mucosal surfaces. In this presentation, a new strategy of global gene expression using avian macrophage (AMM) to characterize the multiple pathways related to the variable immune responses of the host to Eimeria is described. This functional immunogenomics approach will increase current understanding of how mucosal immunity to infectious agents operates, and how it may be enhanced to enable the rational development of new and effective strategies against coccidiosis and other mucosal pathogens.

High-throughput Gene Expression Analysis to Investigate Host-pathogen Interaction in Avian Coccidiosis

Hyun S. Lillehoj 한국가금학회 2007 韓國家禽學會誌 Vol.34 No.1

Application of biotechnological tools for coccidia vaccine development

Hyun S.Lillehoj,Wongi Min,Rami A.Dalloul 대한수의학회 2004 Journal of Veterinary Science Vol.5 No.4

Coccidiosis is a ubiquitous intestinal protozoan infection of poultry seriously impairing the growth and feed utilization of infected animals. Conventional disease control strategies have relied on prophylactic medication. Due to the continual emergence of drug resistant parasites in the field and increasing incidence of broiler condemnations due to coccidia, novel approaches are urgently needed to reduce economic losses. Understanding the basic biology of hostparasite interactions and protective intestinal immune mechanisms, as well as characterization of host and parasite genes and proteins involved in eliciting protective host responses are crucial for the development of new control strategy. This review will highlight recent developments in coccidiosis research with special emphasis on the utilization of cutting edge techniques in molecular/cell biology, immunology, and functional genomics in coccidia vaccine development. The information will enhance our understanding of host-parasite biology, mucosal immunology, and host and parasite genomics in the development of a practical and effective control strategy against Eimeria and design of nutritional interventions to maximize growth under the stress caused by vaccination or infection. Furthermore, successful identification of quantitative economic traits associated with disease resistance to coccidiosis will provide poultry breeders with a novel selection strategy for development of genetically stable, coccidiosis-resistant chickens, thereby increasing the production efficiency.

Postnatal development of T-lymphocyte subpopulations in the intestinal intraepithelium and lamina propria in chickens

Lillehoj, Hyun, S.,Chung, Kyeong S. 충남대학교 약학대학 의약품개발연구소 1992 藥學論文集 Vol.8 No.-

Lillehoj, H.S. and Chung, K.S., l992. Postnatal developmemt of T-lymphocyte subpopulations in the intesinal intraepithelium and lamina propria ln chickens. Vet. Immunol. Immunopathol., 31:347-360. Postnatal development of various T-lymphocyte subpopulations expressing CD3, CD8, CD4, and antigen-specific TCR heterodimers αβ(TCR2) or γδ(TCRl) was investigated in two different inbred chicken strains, SC and TK. The ratios of jejunum T-cells expressing TCRl to TCR2 in the intraepithelium of SC and TK strains gradually increased after hatching and were 3.40 and 4.28 by l2 weeks in TK and SC chickens respectively. The ratios of TCRl^+ to TCR2^+-cells in intraepithelium and the lamina propria in SC chickens were 0.96 and l.23 at 8 weeks and 4.29 and 2.15 at 12 weeks, respectively. Jejunum intraepithelial lymphocytes expressing the CD8 antigen increased gradually until 4-6 weeks of age and subsequently declined as chickens aged. CD4^+-cells represented a minor subpopulalion among the intestinal lymphocyte subpopulations. Therefore, the composition of various T-cell subpopulations in the intestine depended upon host age, the regions of the gut examined and host genetic background. These results suggest that changes in T-cell subpopulations in the intestine may reflect age-related maturation of the gut-associated lymphoid tissues.

Application of DNA Marker Technology and Functional Genomics to the Development of Coccidiosis Control Strategy

Hyun S. Lillehoj,James Zhu,Wongi Min 한국가금학회 2001 한국가금학회 심포지움 Vol.- No.-

Immunological Approaches toward Vaccine Development

Hyun S. Lillehoj 한국생약학회 1989 생약학회지 Vol.20 No.1

Recent Progress in Development of Vaccines against Avian Coccidiosis

Lillehoj, Hyun S. The Korean Society of Poultry Science 1999 韓國家禽學會誌 Vol.26 No.3

Protozoa of the genus Eimeria are the etiologic agents of avian coccidiosis, the most economically important Parasitic disease for the poultry industry. Coccidia multiply in intestinal epithelial cells of a wide range of hosts, including livestock in addition to poultry. Chemotherapy is extensively used to control coccidiosis. However, development of drug resistance by Eimeria parasites, the intensive cost and labor involved in the identification of new anticoccidial compounds and public awareness of drug residues in foods warrant alternative methods to prevent coccidiocic in the fast growing poultry industry. For these reasons, there is a great interest in developing vaccines against avian coccidiosis. Live Eimeria vaccines confer protective immunity, however a significant disadvantage of using these types of vaccines is their pathogenicity. Live parasites with attenuated pathogenicity also usually produce immunity but may revert back to a pathogenic form and may be contaminated with other pathogenic organisms. Killed Eimeria vaccines are safer but, unlike live attenuated vaccines, are not able to generate cytotoxic T lymphocyte responses. Recombinant vaccines are biochemically purified proteins produced by genetic engineering that consist of particular epitopes or metabolites of Eimeria. Unlike live attenuated organisms, recombinant vaccines do not possess as much risk and generally are able to induce both humoral and cell mediated immunity. DNA vaccines consist of genes encoding immunogenic proteins of pathogens that are directly administered into the host in a manner that the gene is expressed and the resulting protein generates a protective immune response. Although all of these different types of vaccines have been applied to coccidiosis, this disease continues to cause substantial morbidity and mortality in the poultry industry. Future development of an effective vaccine against coccidiosis will depend on further investigation of protective immunity to Eimeria infection and identification of important immundgenic parasite molecules.

Alternative drug-free immunomodulation strategies for enteric pathogens

Hyun S. Lillehoj 한국가금학회 2011 한국가금학회 심포지움 Vol.2011 No.5

Expression of Chicken NK-Lysin and Its Role in Chicken Coccidiosis Induced by Eimeria necatrix

Woo Hyun Kim,Wongi Min,Kwang Il Park,Hyun S. Lillehoj,Cherry P. Fernandez-Colorado,Rochelle A. Flores,Paula Leona T. Cammayo,Binh Thanh Nguyen 대한기생충학열대의학회 2021 The Korean Journal of Parasitology Vol.59 No.5