IL-16 Is Critical for Tropheryma whipplei Replication in Whipple’s Disease

Abstract

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 (Mφ) 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 Mφ inhibited bacterial replication. IL-16, which was up-regulated in Mφ, enabled T. whipplei to replicate in monocytes and increased bacterial replication in Mφ. In addition, anti-IL-16 Abs abolished T. whipplei replication in Mφ. 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.

Reduced Peripheral and MucosalTropheryma whipplei-Specific Th1 Response in Patients with Whipple’s Disease

“…This fact explains the deregulated Th1/Th2 response in Whipple's disease we have previously described (14). In addition, untreated Whipple's disease patients reveal elevated serum levels of IL-16 which favors T. whipplei replication in vitro (38). One hypothesis about the role of IL-16 in vivo is that it contributes to a general recruitment of CD4 ϩ T cells in an inflammatory process resulting in cells responsive to cytokine stimulation, but refractory to Ag-specific stimulation (39) because it interferes with cell-mediated immune response (40) and induces tolerogenic dendritic cells (41).…”

“…We studied CD4 ϩ T cell reactivity in 32 patients with different stages of Whipple's disease (13) (Table I, [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]; II, 27 elderly subjects, age-matched to Whipple's disease patients (16 M, 11 F, mean age, 54.9; range, 41-88); and III, 11 active triathletes, agematched to young subjects (11 M, mean age, 32.7; range, [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]. Triathletes practice swimming in the river Neckar in Heidelberg where T. whipplei was detected in sewage plants (5) and thus are supposed to have enhanced contact to environmental T. whipplei.…”

Placental Macrophages Are Impaired in Chorioamnionitis, an Infectious Pathology of the Placenta

“…The purity of the monocytes (CD14 + cells) was determined by flow cytometry and was .98%. To obtain MDMs, monocytes were incubated for 7 d, as described previously (29). More than 95% of the differentiated cells were MDMs, as assessed by CD68 expression and CD14 downmodulation.…”

Vanin‐1 controls granuloma formation and macrophage polarization in Coxiella burnetii infection

“…The fold change in target gene cDNA relative to the bactin endogenous control was determined with the formula: fold change = 2 -DDCt , where DDCt = (Ct TargetCt Actin ) stimulated -(Ct Target -Ct Actin ) unstimulated . Ct values were defined as the cycle numbers at which the fluorescence signals were detected [41]. The transcriptional profile of tissues was determined using the same formula where DDCt = (Ct TargetCt Actin ) infected mice -(Ct Target -Ct Actin ) uninfected mice .…”