Microbial challenges to the host initiate an array of defense processes through the activation of innate and adaptive immunity. Innate immunity consists of sensors or pattern-recognition receptors (PRRs) that are expressed on immune and non-immune cells and sense conserved pathogen-derived molecules or pathogen-associated molecular patterns (PAMPs) in various compartments of the host cells. Recognition of the PAMPs by PRRs triggers antimicrobial effector responses via the induction of proinflammatory cytokines and type I IFNs. Several families of PRRs, such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), and DNA sensors and their respective PAMPs have been well studied in innate immunity and host defense. Here, we review the recent findings on bacterial recognition by TLRs and NLRs and the signaling pathways activated by these sensors.

Innate sensors play a critical role in the early innate immune responses to invading pathogens through sensing of diverse biochemical signatures also known as pathogen associated molecular patterns (PAMPs). These biochemical signatures primarily consist of a major family of biomolecules such as proteins, lipids, nitrogen bases, and sugar and its complexes, which are distinct from host molecules and exclusively expressed in pathogens and essential to their survival. The family of sensors known as pattern recognition receptors (PRRs) are germ-line encoded, evolutionarily conserved molecules, and consist of Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), C-type lectin-like receptors (CLRs), and DNA sensors. Sensing of PAMP by PRR initiates the cascade of signaling leading to the activation of transcription factors, such as NF-κB and interferon regulatory factors (IRFs), resulting in a variety of cellular responses, including the production of interferons (IFNs) and pro-inflammatory cytokines. In this review, we discuss sensing of different types of glycosylated PAMPs such as β-glucan (a polymeric sugar) or lipopolysaccharides, nucleic acid, and so on (sugar complex PAMPs) by different families of sensors, its role in pathogenesis, and its application in development of potential vaccine and vaccine adjuvants.

BackgroundProgrammed Death-1 (PD-1; CD279) receptor molecule is widely believed to be a negative regulator predominantly expressed by exhausted/activated mouse T cells. Upon interaction with its ligands, PD-L1 and PD-L2, PD-1 inhibits activation of T cells and cytokine production, which has been documented in various viral and fungal infections as well as in vitro studies. Therefore, inhibition of T cell responses by PD-1 resulted in disease resistance in a variety of mouse infection models studied heretofore.Methodology/Principal FindingsHere, we report that PD-1 deficient (PD-1−/−) mice infected with Mycobacterium tuberculosis (M. tb) H37Rv by the aerosol route have increased susceptibility as compared with their wild type littermates. Surprisingly, M. tb antigen-specific T cell proliferation was dramatically reduced in PD-1 deficient animals compared with wild-type littermates, and this was due to increased numbers of regulatory T cells (Tregs) and recruitment of mesenchymal stem cells. Furthermore, PD-1−/− mice exhibited decreases in the autophagy-induced LC3-B marker protein in macrophages.Conclusions/SignificanceOur findings suggest that PD-1 does not play an inhibitory role during M. tb infection and instead promotes mycobacterial clearance in mice.

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A series of new 16-membered macrocyclic compounds were synthesized and evaluation of in vitro anti-tumor activities on MDAMB-231 cell lines reveal that the macrocycles, 1a, 1f, 1g, 1i and 1k are promising anti-tumor agents.