The inflammatory-responserelated genes whose expression was highly repressed in PBMCs from M. bovis-infected cattle. It has been reported that CD14 mediates the M. tuberculosis TDM-induced proinflammatory response via SR/toll-like receptors 2. IL-1R encodes a cytokine receptor that belongs to the interleukin 1 receptor family. This protein is a receptor for several cytokines involved in inflammatory responses. Therefore, the downregulation of CD14 and IL-1R expression in M. bovis-infected animals suggests that the bacilli inhibit signaling pathways of antibacterial host defense. Moreover, the expression of CD14 together with the thrombospondin 1 gene is repressed in CD4+ T lymphocytes cocultured with monocytes in response to M. tuberculosis as part of a suppression mechanism induced by suppressor carbohydrates generated from CD8+ T cells. Finally, the repressed FYVE gene encodes a domain found in various proteins including some implicated in vacuolar protein sorting and endosome function. The FYVE domain is implicated in signal transduction and membrane trafficking functions, such as stabilization of the interaction of early endosome antigen 1 with the small GTPase Rab5. However, FYVE domains might have additional functions. Meade et al. analyzed the expression profile of nonstimulated PBMCs from cattle infected with M. bovis. This study has revealed downregulation of the expression of key innate immune genes, including the toll-like receptor 2 and TLR4. Defensins display microbicidal activity against a wide spectrum of Gram-negative and Gram-positive bacteria, fungi and viruses. They are also cytotoxic for epithelial cells and chemotactic for T-cells. Based on the presence of six conserved cysteine residues and sequence homology, human defensins are grouped into a- and b- defensins. The first group includes human neutrophil peptides -1 to 4, major components of the azurophilic granules of GSI-IX Gamma-secretase inhibitor neutrophils, and two enteric human defensins, HD-5 and HD-6, isolated from the granules of Paneth cells in the small intestine. The second group, is mainly expressed in epithelial cells of various organs. It has been shown that ADP-ribosylation of HNP-1 on arginine 14 reduces its antimicrobial and cytotoxic activities. Mono ADP-ribosylation consists in the enzymatic transfer of the single ADP-ribose moiety of NAD to specific amino-acid residues of acceptor proteins coupled to the release of nicotinamide. In mammals this reaction is catalyzed by a family of ADP-ribosyltransferases, while the best studied ADP-ribosylation reactions are those catalyzed by bacterial ADP-ribosylating toxins. The ADP-ribosylation of a large panel of host proteins catalyzed by bacterial toxins leads to the interruption of cellular metabolic and regulatory pathways causing severe diseases. Vibrio cholerae toxin, Escherichia coli heat labile enterotoxin, Pseudomonas aeruginosa exoenzyme S and the recently discovered NarE, a toxin-like protein from Neisseria meningitidis, recognize arginine as an ADP-ribose acceptor in a similar fashion to ART1 and ART5. Arginine specificity is conferred to ARTs by the presence of the R-S-EXE triad signature in the active site. Recent studies indicated that a-defensins display a novel biological function consisting in the ability to neutralize the activity of potent bacterial toxins like lethal factor, a metalloprotease produced by Bacillus anthracis, and toxin B produced by Clostridium difficile. Moreover it has been shown that HNP1-3 neutralize the cytotoxic effects exerted by diphtheria toxin and Pseudomonas aeruginosa exotoxin A, while they were inactive on CT and pertussis toxin.