Is there a link between the human TRIM21 and Trypanosoma cruzi Clone 36 genes in Chagas' disease?
The homology between TRIM21 and Trypanosoma cruzi Antigen Clone 36 nucleotide sequence was discovered in 1998 (Winkler et al., Parasite 5, 94-95) prior to the functions of Ro52, the TRIM21 protein product, being understood. Ro52 has since been shown to be an Ubiquitin ligase targeting transcription factors, Interferon Regulatory Factor 1 (IRF1) and Interferon Regulatory Factor 3 (IRF3), in immune cells. This communication explores the possibility that there is a connection between the Clone 36 homologous sequence and perturbation of the host immune system in Chagas' disease. RNA interference by the Clone 36 transcripts is hypothesized as a mechanism for host immune suppression during acute Chagas' disease and/or for autoimmunity in chronic Chagas' disease through down-regulation of Ro52. In the chronic forms of the disease such as Chagas Cardiomyopathy, Clone 36 RNA containing its repetitive motif may down-regulate levels of Ro52 in monocytes, fibroblasts, or T cells, allowing IRF 1 and IRF3 to continuously stimulate transcription of interferons alpha and beta, a pro-inflammatory state favoring autoimmunity. In acute Chagas' disease, messenger RNA from Clone 36 could interfere with host macrophage Ro52 RNA, down-regulating the level of Ro52 so that it would stimulate less cytokine production, including IL-12/p40. This theory is thought to help the parasite avoid attack by the innate immune system early in the acute phase of the disease. Experiments with transgenic mice and genetically modified T. cruzi are discussed which may provide insight to addressing these questions.
Winkler
Martin A
MA
Biotech Advisor, 1995 Via Tesoro, Las Cruces, NM 88005-8211, USA. winklerm@phoenix.edu
Pan
Alfred A
AA
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D014355:Chagas Disease / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000032:analysis; D012261:Ribonucleoproteins / Q000235:genetics* / Q000276:immunology*; D012689:Sequence Homology, Nucleic Acid; D014349:Trypanosoma cruzi / Q000235:genetics* / Q000276:immunology*; D000099207:SS-A Antigen
D000953:Antigens, Protozoan; D012367:RNA, Viral; D012261:Ribonucleoproteins; D000099207:SS-A Antigen