Highlights d TREM2 is expressed by tumor-associated macrophages in different types of tumors d TREM2 deficiency and anti-TREM2 mAb treatment both curb tumor growth in mice d Anti-PD-1 treatment is more efficacious when TREM2 is either absent or engaged by a mAb d Modulation of TREM2 remodels the tumor macrophage landscape

Innate lymphoid cells (ILCs) are innate counterparts of T cells that contribute to immune responses by secreting effector cytokines and regulating the functions of other innate and adaptive immune cells. ILCs carry out some unique functions but share some tasks with T cells. ILCs are present in lymphoid and non-lymphoid organs and are particularly abundant at the mucosal barriers, where they are exposed to allergens, commensal microbes, and pathogens. The impact of ILCs in mucosal immune responses has been extensively investigated in the gastrointestinal and respiratory tracts, as well as in the oral cavity. Here we review the state-of-the-art knowledge of ILC functions in infections, allergy and autoimmune disorders of the mucosal barriers.

BackgroundErythrocyte-associated antigenic polymorphisms or their absence have perhaps evolved in the human population to protect against malarial infection. Studies in various populations consistently demonstrate that blood group 'O' confers resistance against severe falciparum infection. In India, Odisha state has one of the highest incidences of Plasmodium falciparum infection and contributes to the highest number of deaths by falciparum malaria. This study aims to evaluate the relationship between ABO blood group and severe malaria in an adult population at the tertiary care centre in Odisha.MethodsA total of 353 P. falciparum infected subjects and 174 healthy controls were screened for ABO blood group. Falciparum-infected individuals were categorized as severe malaria and uncomplicated malaria. Severe malaria was further clinically phenotyped into cerebral malaria, non-cerebral severe malaria and multi-organ dysfunction. A meta-analysis was performed to assess the role of ABO blood group in severe malaria.ResultsFrequency of blood group 'B' was significantly higher in patients with severe malaria compared to the uncomplicated cases (P < 0.0001; OR = 4.09) and healthy controls (P < 0.0001; OR = 2.79). Irrespective of the level of clinical severity, blood group 'B' was significantly associated with cerebral malaria (P < 0.0001; OR = 5.95), multi-organ dysfunction (P < 0.0001; OR = 4.81) and non-cerebral severe malaria patients (P = 0.001; OR = 3.02) compared to the uncomplicated category. Prevalence of 'O' group in uncomplicated malaria (P < 0.0001; OR = 2.81) and healthy controls (P = 0.0003; OR = 2.16) was significantly high compared to severe malaria. Meta-analysis of previous studies, including the current one, highlighted the protective nature of blood group 'O' to severe malaria (P = 0.01). On the other hand, carriers of blood group 'A' (P = 0.04) and 'AB' (P = 0.04) were susceptible to malaria severity.ConclusionsResults of the current study indicate that blood group 'O' is associated with reduced and 'B' blood group with increased risk of development of severe malaria in Odisha, India. Meta-analysis also supports the protective nature of blood group 'O' from severe falciparum infection.

Sepsis is a consequence of systemic bacterial infections leading to hyper activation of immune cells by bacterial products resulting in enhanced release of mediators of inflammation. Endotoxin (LPS) is a major component of the outer membrane of Gram negative bacteria and a critical factor in pathogenesis of sepsis. Development of antagonists that inhibit the storm of inflammatory molecules by blocking Toll like receptors (TLR) has been the main stay of research efforts. We report here that a filarial glycoprotein binds to murine macrophages and human monocytes through TLR4 and activates them through alternate pathway and in the process inhibits LPS mediated classical activation which leads to inflammation associated with endotoxemia. The active component of the nematode glycoprotein mediating alternate activation of macrophages was found to be a carbohydrate residue, Chitohexaose. Murine macrophages and human monocytes up regulated Arginase-1 and released high levels of IL-10 when incubated with chitohexaose. Macrophages of C3H/HeJ mice (non-responsive to LPS) failed to get activated by chitohexaose suggesting that a functional TLR4 is critical for alternate activation of macrophages also. Chitohexaose inhibited LPS induced production of inflammatory molecules TNF-α, IL-1β and IL-6 by macropahges in vitro and in vivo in mice. Intraperitoneal injection of chitohexaose completely protected mice against endotoxemia when challenged with a lethal dose of LPS. Furthermore, Chitohexaose was found to reverse LPS induced endotoxemia in mice even 6/24/48 hrs after its onset. Monocytes of subjects with active filarial infection displayed characteristic alternate activation markers and were refractory to LPS mediated inflammatory activation suggesting an interesting possibility of subjects with filarial infections being less prone to develop of endotoxemia. These observations that innate activation of alternate pathway of macrophages by chtx through TLR4 has offered novel opportunities to cell biologists to study two mutually exclusive activation pathways of macrophages being mediated through a single receptor.

The objective of this systematic review and meta-analysis was to determine the clinical effectiveness of bulk-fill and conventional resin in composite restorations. A bibliographic search was carried out until May 2020, in the biomedical databases Pubmed/MEDLINE, EMBASE, Scopus, CENTRAL and Web of Science. The study selection criteria were: randomized clinical trials, in English, with no time limit, with a follow-up greater than or equal to 6 months and that reported the clinical effects (absence of fractures, absence of discoloration or marginal staining, adequate adaptation marginal, absence of post-operative sensitivity, absence of secondary caries, adequate color stability and translucency, proper surface texture, proper anatomical form, adequate tooth integrity without wear, adequate restoration integrity, proper occlusion, absence of inflammation and adequate point of contact) of restorations made with conventional and bulk resins. The risk of bias of the study was analyzed using the Cochrane Manual of Systematic Reviews of Interventions. Sixteen articles were eligible and included in the study. The results indicated that there is no difference between restorations with conventional and bulk resins for the type of restoration, type of tooth restored and restoration technique used. However, further properly designed clinical studies are required in order to reach a better conclusion.

Uncontrolled secretion of type I IFN, as the result of endosomal TLR (i.e., TLR7 and TLR9) signaling in plasmacytoid DCs (pDCs), and abnormal production of autoantibodies by B cells are critical for systemic lupus erythematosus (SLE) pathogenesis. The importance of galectin-9 (Gal-9) in regulating various autoimmune diseases, including lupus, has been demonstrated. However, the precise mechanism by which Gal-9 mediates this effect remains unclear. Here, using spontaneous murine models of lupus (i.e., BXSB/MpJ and NZB/W F1 mice), we demonstrate that administration of Gal-9 results in reduced TLR7-mediated autoimmune manifestations. While investigating the mechanism underlying this phenomenon, we observed that Gal-9 inhibits the phenotypic maturation of pDCs and B cells and abrogates their ability to mount cytokine responses to TLR7/TLR9 ligands. Importantly, immunocomplex-mediated (IC-mediated) and neutrophil extracellular trap-mediated (NET-mediated) pDC activation was inhibited by Gal-9. Additionally, the mTOR/p70S6K pathway, which is recruited by both pDCs and B cells for TLR-mediated IFN secretion and autoantibody generation, respectively, was attenuated. Gal-9 was found to exert its inhibitory effect on both the cells by interacting with CD44.

Background Current evidence on vertical transmission of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) and neonatal outcome among exposed newborns is emerging and posing a challenge for preventive interventions. Perinatal transmission to the neonates especially during breastfeeding and rooming in is also relatively unknown. Methods This prospective observational study was conducted in Kalinga Institute of Medical Science (KIMS), Odisha state from 1 st May to 20 th October 2020. A total of 165 neonates born to SARS-CoV-2 infected mothers were enrolled. Real time polymerase chain reaction (RT PCR) testing was done in first 32 neonates in initial 24 hours of life. Results The clinical characteristics of 162 mothers & 165 neonates were analyzed. Mode of delivery was by caesarian section in most (n=103, 60%) cases. Three (3/32, 9.4%) inborn and 6 outborn neonates were SARS-CoV-2 positive. Thirty-eight (23%) babies needed neonatal intensive care. Clinical characteristics of neonates were meconium-stained amniotic fluid (MSAF, [23.63%]), prematurity (16.9%), respiratory distress (10.5%), moderate to severe hypoxic ischemic encephalopathy (3.6%), sepsis (7%) and hyperbilirubinemia (8.7%). Out of 138 stable babies kept on mother side and initiated breast feeding, none of them developed any signs and symptoms attributable to SARS-CoV-2. Five (3%) neonates died in COVID hospital of which one baby was SARS-CoV-2 positive. Conclusion There was an increased rate of incidences of hypoxic ischemic encephalopathy, meconium stained liquor and cesarean section delivery in COVID hospital. We found a possible vertical transmission in 9.4% cases. None of the neonates developed sign and symptoms of SARS-CoV-2 infection during rooming in and breast feeding.

In Gram-negative bacterial sepsis, production of excess pro-inflammatory cytokines results in hyperinflammation and tissue injury. Anti-inflammatory cytokines such as IL-10 inhibit inflammation and enhance tissue healing. Here, we report a novel approach to treat septicemia associated with intra-abdominal infection in a murine model by delicately balancing pro- and anti-inflammatory cytokines. A novel oligosaccharide compound AVR-25 selectively binds to the TLR4 protein (IC 50 = 0.15 µM) in human peripheral blood monocytes and stimulates IL-10 production. Following the cecal ligation and puncture (CLP) procedure, intravenous dosing of AVR-25 (10 mg/kg, 6–12 h post-CLP) alone and in combination with antibiotic imipenem protected both young adult (10–12 week old) and aged (16–18 month old) mice against polymicrobial infection, organ dysfunction, and death. Proinflammatory cytokines (TNF-α, MIP-1, i-NOS) were decreased significantly and restoration of tissue damage was observed in all organs. A decrease in serum C-reactive protein (CRP) and bacterial colony forming unit (CFU) confirmed improved bacterial clearance. Together, these findings demonstrate the therapeutic ability of AVR-25 to mitigate the storm of inflammation and minimize tissue injury with high potential for adjunctive therapy in intra-abdominal sepsis.