Biomedical subjects

Sucharitha Balu

Publications and source records attributed to Sucharitha Balu.

4 recordsLinked to original sources

PubMed2006

Infectious bursal disease virus: strains that differ in virulence differentially modulate the innate immune response to infection in the chicken bursa.

Little is understood about the immune responses involved in the pathogenesis of infectious bursal disease virus (IBDV). Strains of IBDV differ in their virulence: F52/70 is a classical virulent strain (vIBDV), whereas UK661 is a very virulent strain (vvIBDV) that causes greater pathology and earlier mortality. The exact causes of clinical disease and death are still unclear. Pro-inflammatory cytokines such as interleukin (IL)-1beta and IL-6, produced by activated macrophages, could play a role, as could cytokines produced by T and natural killer (NK) cells, such as interferon (IFN)-gamma, which stimulate macrophages. We quantified mRNA transcription in bursal tissue, by real-time quantitative reverse transcription- polymerase chain reaction (RT-PCR), for the type I IFN (IFN-alpha and IFN-beta), pro-inflammatory cytokines (IL-1beta, IL-6, and CXCLi2), the anti-inflammatory cytokine transforming growth factor (TGF)-beta4, and Th1 cytokines (IFN-gamma, IL-2 [and the closely related IL-15], IL-12, and IL-18) for the first 5 days after infection of 3-week-old chickens with F52/70 or UK661 and compared these with levels in bursal tissue from uninfected age-matched controls. Both strains induced a pro-inflammatory response, evidenced by increased mRNA transcription of IL-1beta, IL-6, and CXCLi2, and down-regulation of TGF-beta4, of similar magnitude and timing. IFN-gamma mRNA was induced by both strains, although to a greater degree by the vvIBDV strain, indicating that a cell-mediated response is induced. Neither virus initially induced high levels of type I IFN. F52/70 seems to use a "stealth" approach by not inducing the type I IFNs, whereas UK661 down-regulates their expression. This suggests that both viruses modulate the host immune response, although probably by using different mechanisms.

Animals↗

PubMed2005

A genomic analysis of chicken cytokines and chemokines.

As most mechanisms of adaptive immunity evolved during the divergence of vertebrates, the immune systems of extant vertebrates represent different successful variations on the themes initiated in their earliest common ancestors. The genes involved in elaborating these mechanisms have been subject to exceptional selective pressures in an arms race with highly adaptable pathogens, resulting in highly divergent sequences of orthologous genes and the gain and loss of members of gene families as different species find different solutions to the challenge of infection. Consequently, it has been difficult to transfer to the chicken detailed knowledge of the molecular mechanisms of the mammalian immune system and, thus, to enhance the already significant contribution of chickens toward understanding the evolution of immunity. The availability of the chicken genome sequence provides the opportunity to resolve outstanding questions concerning which molecular components of the immune system are shared between mammals and birds and which represent their unique evolutionary solutions. We have integrated genome data with existing knowledge to make a new comparative census of members of cytokine and chemokine gene families, distinguishing the core set of molecules likely to be common to all higher vertebrates from those particular to these 300 million-year-old lineages. Some differences can be explained by the different architectures of the mammalian and avian immune systems. Chickens lack lymph nodes and also the genes for the lymphotoxins and lymphotoxin receptors. The lack of functional eosinophils correlates with the absence of the eotaxin genes and our previously reported observation that interleukin- 5 (IL-5) is a pseudogene. To summarize, in the chicken genome, we can identify the genes for 23 ILs, 8 type I interferons (IFNs), IFN-gamma, 1 colony-stimulating factor (GM-CSF), 2 of the 3 known transforming growth factors (TGFs), 24 chemokines (1 XCL, 14 CCL, 8 CXCL, and 1 CX3CL), and 10 tumor necrosis factor superfamily (TNFSF) members. Receptor genes present in the genome suggest the likely presence of 2 other ILs, 1 other CSF, and 2 other TNFSF members.

Amino Acid Sequence↗

PubMed2004

Evolution of the interleukins.

As the adaptive immune system arose in jawed vertebrates, a reasonable working hypothesis is that cytokines involved exclusively in controlling the adaptive immune system, e.g. T1 and T2 cytokines, will only be found in jawed vertebrates whilst those with a role in innate responses, e.g. type I IFNs or pro-inflammatory cytokines, will be universal, or have functional equivalents in 'lower' animals. Progress to date in cloning cytokines, including interleukins, in vertebrates outside of mammals is limited and non-existent in invertebrates. T1 and T2 interleukins have only been cloned in birds. Receptors for T1 and T2 interleukins have been cloned in fish, however, suggesting the presence of the corresponding interleukins. Pro-inflammatory interleukins have been cloned in birds, fish and amphibia, but not reptiles. Cross-reactive bioassays, polyclonal antisera and mAbs suggest that an IL-6-like factor exists in starfish, as yet the only evidence for innate immune response cytokines in 'lower' animals.

Amino Acid Sequence↗

PubMed2003

Avian interleukin-12beta (p40): cloning and characterization of the cDNA and gene.

We isolated the chicken interleukin-12 (ChIL-12) p40 cDNA from a concanavalin A (ConA)-stimulated spleen cDNA library using the PCR with primers based on a partial 3' EST sequence in a chicken EST library. The cDNA encodes a polypeptide of 315 amino acids (aa), with a predicted mature peptide of 300 aa. ChIL-12 p40 has 46% and 41% amino acid identity with human (HuIL-12) and murine IL-12 (MuIL-12) p40, respectively. We also isolated a partial turkey IL-12 (TuIL-12) p40 cDNA sequence with 95% predicted aa identity with ChIL-12 p40. The structures of the ChIL-12 p40 gene and its promoter were determined by direct sequencing of a chicken BAC identified by hybridization with the cDNA. The gene structures of HuIL-12, MuIL-12, and ChIL-12 p40 all differ. The promoter of the ChIL-12 p40 gene shares some (an ETS consensus sequence, a C/EBP binding site, and a TATA box) but not all (an NF-kappaB binding site and a GA12 site are absent) of the transcription factor binding sites identified in the human and murine promoters. IL-12 p40 mRNA expression was identified in a wide variety of tissues and in B, T, and macrophage cell lines by RT-PCR.

Amino Acid Sequence↗