A total of 1 × 105 reporter cells (L929, no. CCL-1; American Type Tissue Collection,

Manassas, VA, USA) were cultured with 15% wild-type BMN-673 or Irf5-deficient serum for 6 h and total cellular mRNA isolated. Reverse-transcription and qPCR were performed as described above with primers for murine IRF7 (F: 5-GACCTTGGATCTACTGTGG-3 and R: 5-TAGAAAGCAGAGGGCTTG-3) and b-actin. The delta Ct method was used to calculate relative IRF7 expression. For normally distributed variables, differences between groups were analyzed by the Student’s t-test. For variables not normally distributed, the Mann–Whitney U test was used. Normality was assessed by the Shapiro–Wilk test. Data are presented as mean ± SD (normal distribution) or buy Palbociclib mean ± SEM (nonnormal distribution). p value < 0.05 was considered significant. Statistical analyses were performed using Prism 4.0 (GraphPad Software, San Diego, CA, USA). We thank I. Rifkin for providing the Irf5-deficient mice by approval from Tadatsugu Tanaguchi and Tak Mak. We thank R. Donnelly for help with the Luminex assays. This work was supported by grants from the National Institute of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; 5R03AR054070) and the Arthritis Foundation (to B.J.B.). The authors declare no financial or commercial conflict of interest. Disclaimer: Supplementary materials have

been peer-reviewed but not copyedited. “
“Neurotrophic receptors TrkA and TrkC double up as tuclazepam receptors that Trypanosoma cruzi uses to invade cells and as autoantigen

in T. cruzi-infected individuals (with Chagas’ disease). Consequently, autoantibodies against TrkA and TrkC (ATA) potently block T. cruzi invasion in vitro and in ATA-immunized mice. Thus, ATA could keep T. cruzi invasion in check in Chagas’ disease. However, ATA has been examined only in patients with chronic Chagas’ disease. To determine whether ATA potentially participate in the early stage of infection, we analysed the sera of 15 patients with acute Chagas’ disease, 4–66 years of age. We find that all sera contain high antibody titres to TrkA, TrkB and TrkC, but not to other growth factor receptors, indicating that ATA are produced relatively soon after T. cruzi infection by an age-independent process. One individual, who acquired the disease after an accidental laboratory infection, converted to Trk-antibody (Ab)-seronegative when progressing to the chronic phase. ATA from acute patients were of low avidity (K0 <24.8 × 10−8 m) and of IgM and IgA isotypes. In contrast, ATA from chronic patients were of high avidity (Ko = 1.4 to 4.5 × 10−8 m) and of the IgG2 isotype. Therefore, ATA underwent affinity maturation and class switch when patients progressed from acute to chronic disease. Thus, it may be that Trk autoimmunity, which starts in the acute Chagas’ disease, plays a role in attenuating parasitemia and tissue parasitism that characterizes the acute/chronic phase transition of Chagas’ disease.