IL-16 is critical for Tropheryma whipplei replication in Whipple's disease.
Whipple's disease (WD) is a rare systemic disease caused by Tropheryma whipplei. We showed that T. whipplei was eliminated by human monocytes but replicated in monocyte-derived macrophages (Mphi) by inducing an original activation program. Two different host molecules were found to be key elements for this specific pattern. Thioredoxin, through its overexpression in infected monocytes, was involved in bacterial killing because adding thioredoxin to infected Mphi inhibited bacterial replication. IL-16, which was up-regulated in Mphi, enabled T. whipplei to replicate in monocytes and increased bacterial replication in Mphi. In addition, anti-IL-16 Abs abolished T. whipplei replication in Mphi. IL-16 down-modulated the expression of thioredoxin and up-regulated that of IL-16 and proapoptotic genes. In patients with WD, T. whipplei replication was higher than in healthy subjects and was related to high levels of circulating IL-16. Both events were corrected in patients who successfully responded to antibiotics treatment. This role of IL-16 was not reported previously and gives an insight into the understanding of WD pathophysiology.
Desnues
Benoît
B
Unité des Rickettsies, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6020, Institut Fédératif de Recherche 48, Université de la Méditerranée, Faculté de Médecine, Marseille, France.
Raoult
Didier
D
Mege
Jean-Louis
JL
D000192:Actinomycetales / Q000166:cytology* / Q000254:growth & development*; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D019410:Interleukin-16 / Q000502:physiology*; D008264:Macrophages / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000382:microbiology; D013879:Thioredoxins / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D008061:Whipple Disease / Q000378:metabolism / Q000382:microbiology*
D019410:Interleukin-16; D013879:Thioredoxins