Screening for Toxoplasma gondii-regulated transcriptional responses in lipopolysaccharide-activated macrophages.
Toxoplasma gondii-infected macrophages are blocked in production of the proinflammatory cytokines interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-alpha) upon activation with lipopolysaccharide (LPS). Here, we used pathway-focused cDNA arrays to identify additional T. gondii-regulated transcriptional responses. Parasite infection decreased 57 (inclusive of IL-12 and TNF-alpha) and increased expression of 7 of 77 LPS-activated cytokine and cytokine-related genes. Interestingly, we found that the LPS-induced transcriptional response of the anti-inflammatory cytokine IL-10 was synergistically increased by T. gondii, results that we validated by conventional reverse transcription-PCR and enzyme-linked immunosorbent assay. Importantly, although the parasite exerted disparate effects in LPS-signaling leading to TNF-alpha versus IL-10 production, both responses required functional Toll-like receptor 4. We suggest that these effects represent parasite defense mechanisms to avoid or delay induction of antimicrobial activity and/or T-cell-mediated immunity during Toxoplasma infection.
Lee
Chiang W
CW
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853-6401, USA.
Bennouna
Soumaya
S
Denkers
Eric Y
EY
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000469:parasitology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D014122:Toxoplasma / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*
D008070:Lipopolysaccharides; D016753:Interleukin-10