Biomedical subjects

Adrian L Smith

Publications and source records attributed to Adrian L Smith.

3 recordsLinked to original sources

PubMed2003

Allelic variation in TLR4 is linked to susceptibility to Salmonella enterica serovar Typhimurium infection in chickens.

Toll-like receptor 4 (TLR4) is part of a group of evolutionarily conserved pattern recognition receptors involved in the activation of the immune system in response to various pathogens and in the innate defense against infection. We describe here the cloning and characterization of the avian orthologue of mammalian TLR4. Chicken TLR4 encodes a 843-amino-acid protein that contains a leucine-rich repeat extracellular domain, a short transmembrane domain typical of type I transmembrane proteins, and a Toll-interleukin-1R signaling domain characteristic of all TLR proteins. The chicken TLR4 protein shows 46% identity (64% similarity) to human TLR4 and 41% similarity to other TLR family members. Northern blot analysis reveals that TLR4 is expressed at approximately the same level in all tissues tested, including brain, thymus, kidney, intestine, muscle, liver, lung, bursa of Fabricius, heart, and spleen. The probe detected only one transcript of ca. 4.4 kb in length for all tissues except muscle where the size of TLR4 mRNA was ca. 9.6 kb. We have mapped TLR4 to microchromosome E41W17 in a region harboring the gene for tenascin C and known to be well conserved between the chicken and mammalian genomes. This region of the chicken genome was shown previously to harbor a Salmonella susceptibility locus. By using linkage analysis, TLR4 was shown to be linked to resistance to infection with Salmonella enterica serovar Typhimurium in chickens (likelihood ratio test of 10.2, P = 0.00138), suggesting a role of TLR4 in the host response of chickens to Salmonella infection.

Alleles↗

PubMed2002

Experimental models linking dendritic cell lineage, phenotype and function.

One of the important issues in dendritic cell (DC) biology today is how DC control the fate of T cells. Our data suggest that an important branch point in determining T cell fate is the decision between deletion and memory. We have previously hypothesized that this binary decision is determined by contact with DC derived from lymphoid- versus myeloid-restricted progenitors. However, the false attribution of CD8alpha expression as a reliable marker of lymphoid origin has underpinned a number of studies in which DC expressing CD8alpha did not induce deletion, thereby clouding the issue of whether deletion is indeed a function of lymphoid DC. By returning to basics, that is, functional testing of the progeny of lymphoid- and myeloid-restricted progenitors in vivo, we hope to provide clear evidence of the in vivo roles of lymphoid and myeloid DC subsets, independent of assumptions about the surface phenotypes they can assume.

Animals↗

PubMed2002

Antigenic diversity in Eimeria maxima and the influence of host genetics and immunization schedule on cross-protective immunity.

Eimeria spp. are a group of highly successful intracellular protozoan parasites that develop within enterocytes. Eimeria maxima from the chicken is characterized by high immunogenicity (a small priming infection gives complete immunity to subsequent homologous challenge) and naturally occurring antigenically variant populations that do not completely cross-protect. In this study we examined the expression of antigenic diversity in E. maxima, as manifested by cross-strain protection in a series of inbred chicken lines. The IAH line of Light Sussex chickens and all lines of inbred White Leghorns were susceptible to primary infections with either of two strains (H and W) of E. maxima and were protected completely against challenge with the homologous strain of parasite. The extent of cross-protection against the heterologous parasite strain varied from 0 to almost 100% depending on host genetics. Interestingly, in one inbred line of chickens (line 15I) the cross-protective phenotype was directional and intensely influenced by the infection history of the host. The basis for the observed variation in cross-protection is not known, but our results suggest that the major histocompatibility complex is not a major genetic component of the phenotype. These results are discussed in relation to the number of protective antigens presented by complex pathogens and the development of immunoprotective responses in hosts of different genetic backgrounds.

Animals↗