Inflammatory bowel disease (IBD), which comprises ulcerative colitis and Crohn's disease, is an immune-mediated, chronic-relapsing, disabling disorder which is associated with increased mortality and poor patients' quality of life. Patients with IBD are at increased risk of infections for many reasons.  https://www.selleckchem.com/products/GDC-0449.html  In fact, IBD often requires a lifelong immunosuppressive and/or biologic therapy, both commonly associated with respiratory and opportunistic infections, but also gastrointestinal, urinary tract infections, and sepsis. Moreover, impaired spleen function has been found in a considerable proportion of IBD patients, further increasing the risk of developing infections sustained by encapsulated bacteria, such as S. pneumoniae, H. influenzae, and N. meningitidis. Finally, comorbidities and surgery represent additional risk factors for these patients. Despite the availability of vaccinations against the most common serotypes of encapsulated bacteria, uncertainties still exist regarding a proper vaccination strategy and the actual effectiveness of vaccinations in this particular setting. Aim of this narrative review is to focus on the broad topic of vaccinations against encapsulated bacteria in IBD patients, discussing the clinical impact of infections, predisposing factors, vaccinations strategies, and unmet research and clinical needs. Copyright © 2020 Lenti, Mengoli, Vernero, Aronico, Conti, Borrelli de Andreis, Cococcia and Di Sabatino.Psoriasis is a chronic, inflammatory disease affecting the skin and joints. The pathogenesis of this disease is associated with genetic, environmental and immunological factors, especially unbalanced T cell activation and improper keratinocyte differentiation. Psoriatic lesion infiltrate is composed of monocytes and T cells, and most studies have focused on the participation of T cells in the pathogenesis of this disease. Here we investigated the contribution of mononuclear phagocytes in the immunopathology observed in psoriatic patients. Significant increases in the levels of TNF, IL-1β, CXCL9, as well as the soluble forms of CD14 and CD163, were observed within the lesions of psoriatic patients compared to skin biopsies obtained from healthy individuals. Moreover, we found an association between the levels of CCL2, a monocyte attractant chemokine, and disease severity. In conclusion, our findings suggest a potential role for mononuclear phagocytes in the pathogenesis of psoriasis. Copyright © 2020 Costa, Paixão, Viana, Rocha, Saldanha, da Mota, Machado, Pagliari, de Oliveira, Arruda, Carvalho and Carvalho.The generation of a potent humoral immune response by B cells relies on the integration of signals induced by the B cell receptor, toll-like receptors and both negative and positive co-receptors. Several reports also suggest that integrin signaling plays an important role in this process. How integrin signaling is regulated in B cells is however still partially understood. Integrin activity and function are controlled by several mechanisms including regulation by molecular adaptors of the paxillin family. In B cells, Leupaxin (Lpxn) is the most expressed member of the family and in vitro studies suggest that it could dampen BCR signaling. Here, we report that Lpxn expression is increased in germinal center B cells compared to naïve B cells. Moreover, Lpxn deficiency leads to decreased B cell differentiation into plasma cells in vitro. However, Lpxn seems dispensable for the generation of a potent B cell immune response in vivo. Altogether our results suggest that Lpxn is dispensable for T-dependent and T-independent B cell immune responses. Copyright © 2020 Bonaud, Clare, Bisio, Sowerby, Yao, Ostergaard, Balabanian, Smith and Espéli.Resistance toward current and new classes of anti-tuberculosis (anti-TB) antibiotics are rapidly emerging; thus, innovative therapies focused on host processes, termed host-directed therapies (HDTs), are promising novel approaches for shortening therapy regimens without inducing drug resistance. Development of new TB drugs is lengthy and expensive, and success is not guaranteed; thus, alternatives are needed. Repurposed drugs have already passed Food and Drug Administration (FDA) as well as European Medicines Agency (EMA) safety requirements and may only need to prove efficacy against Mycobacterium tuberculosis (M.tb). Phosphodiesterases (PDEs) hydrolyze the catalytic breakdown of both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) to their inactive mononucleotides. Advances in molecular pharmacology have identified 11 PDE families; and the success of sildenafil, a PDE-5 selective inhibitor (PDE-5i), in treating pulmonary hypertension and erectile dysfunction has invigorated research into the therapeutic potential of selective PDE inhibitors in other conditions. Myeloid-derived suppressor cells (MDSCs) suppress anti-TB T-cell responses, likely contributing to TB disease progression. PDE-5i increases cGMP within MDSC resulting in the downregulation of arginase-1 (ARG1) and nitric oxide synthase 2 (NOS2), reducing MDSC's suppressive potential. The effect of this reduction decreases MDSC-induced T-cell-suppressive mechanisms. This review highlights the possibility of HDT targeting of MDSC, using a PDE-5i in combination with the current TB regimen, resulting in improved TB treatment efficacy. Copyright © 2020 Leukes, Walzl and du Plessis.NKG2D is an activating receptor expressed by NK cells and some subsets of T cells and represents a major recognition receptor for detection and elimination of cancer cells. The ligands of NKG2D are stress-induced self-proteins that can be secreted as soluble molecules by protease-mediated cleavage. The release of NKG2D ligands in the extracellular milieu is considered a mode of finely controlling their surface expression levels and represents a relevant immune evasion mechanism employed by cancer cells to elude NKG2D-mediated immune surveillance. A disintegrin and metalloproteinase 10 (ADAM10), a catalytically active member of the ADAM family of proteases, is involved in the cleavage of some NKG2D ligands in various types of cancer cells either in steady state conditions and in response to an ample variety of stress stimuli. Appealing immunotherapeutic strategies devoted to promoting NK cell-mediated recognition and elimination of cancer cells are based on the upregulation of NK cell activating ligands. In particular, activation of DNA damage response (DDR) and the induction of cellular senescence by chemotherapeutic agents are associated with increased expression of NKG2D ligands on cancer cell surface.