BACKGROUND: Sponges (phylum Porifera) constantly interact with microbes. They graze on microbes from the water column by filter-feeding and they harbor symbiotic partners within their bodies. In experimental setups, sponges take up symbionts at lower rates compared with seawater microbes. This suggests that sponges have the capacity to differentiate between microbes and preferentially graze in non-symbiotic microbes, although the underlying mechanisms of discrimination are still poorly understood. Genomic studies showed that, compared to other animal groups, sponges present an extended repertoire of immune receptors, in particular NLRs, SRCRs, and GPCRs, and a handful of experiments showed that sponges regulate the expression of these receptors upon encounter with microbial elicitors. We hypothesize that sponges may rely on differential expression of their diverse repertoire of poriferan immune receptors to sense different microbial consortia while filter-feeding. To test this, we characterized the transcriptomic response of two sponge species, Aplysina aerophoba and Dysidea avara, upon incubation with microbial consortia extracted from A. aerophoba in comparison with incubation with seawater microbes. The sponges were sampled after 1 h, 3 h, and 5 h for RNA-Seq differential gene expression analysis.
RESULTS: D. avara incubated with A. aerophoba-symbionts regulated the expression of genes related to immunity, ubiquitination, and signaling. Within the set of differentially-expressed immune genes we identified different families of Nucleotide Oligomerization Domain (NOD)-Like Receptors (NLRs). These results represent the first experimental evidence that different types of NLRs are involved in microbial discrimination in a sponge. In contrast, the transcriptomic response of A. aerophoba to its own symbionts involved comparatively fewer genes and lacked genes encoding for immune receptors.
CONCLUSIONS: Our work suggests that: (i) the transcriptomic response of sponges upon microbial exposure may imply \"fine-tuning\" of baseline gene expression as a result of their interaction with microbes, (ii) the differential response of sponges to microbial encounters varied between the species, probably due to species-specific characteristics or related to host\'s traits, and (iii) immune receptors belonging to different families of NLR-like genes played a role in the differential response to microbes, whether symbionts or food bacteria. The regulation of these receptors in sponges provides further evidence of the potential role of NLRs in invertebrate host-microbe interactions. The study of sponge responses to microbes exemplifies how investigating different animal groups broadens our knowledge of the evolution of immune specificity and symbiosis.

OBJECTIVE: Endometriosis is a prevalent chronic gynecological disease linked to immune dysfunction. The protein T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) plays a crucial role in immune system balance. Malfunction of TIM-3 may result in excessive immune activation and inflammatory tissue damage. Given TIM-3\'s established role in the development of cancer and autoimmune diseases, we decided to study its role in women suffering from endometriosis.
METHODS: We included a total of 62 female patients, all of whom had undergone laparoscopic surgery. Of these, 47 had endometriosis and 15 did not. During surgery, we collected peritoneal fluid (PF) and peripheral blood (PB) samples from every patient for analysis using flow cytometry. To mark the samples, we used a panel of monoclonal antibodies and examined TIM-3 expression in their immune cells.
RESULTS: Endometriosis patients in PB demonstrated a significantly lower percentage of CD56+ T cells with TIM-3 expression. As endometriosis progressed through its stages, this expression lessened. This decrease was particularly notable in women with stage III/IV endometriosis. Additionally, both women diagnosed with intestinal endometriosis and those with recent endometriosis diagnoses showed a significantly reduced percentage of CD56+ T cells expressing TIM-3.
CONCLUSIONS: Patients with endometriosis exhibit diminished TIM-3 expression within circulating T cells. This warrants further investigation to discern whether it contributes to the progression of endometriosis, potentially through the amplification of autoreactive T cells and inflammation.

Autophagy dysfunction has been closely related with pathogenesis of many neurodegenerative diseases and therefore represents a potential therapeutic target. Extracellular vesicles (EVs) may act as potent anti-inflammatory agents and also modulators of autophagy in target cells. However, the molecular mechanisms by which EVs modulate autophagy flux in human microglia remain largely unexplored. In the present study, we investigated the effects of EVs derived from human oral mucosa stem cells on the autophagy in human microglia. We demonstrate that EVs promoted autophagy and autophagic flux in human microglia and that this process was dependent on the integrity of lipid rafts. Lipopolysaccharide (LPS) also activated autophagy, but combined treatment with EVs and LPS suppressed autophagy response, indicating interference between these signaling pathways. Blockage of Toll-like receptor 4 (TLR4) with anti-TLR4 antibody suppressed EV-induced autophagy. Furthermore, inhibition of the EV-associated heat shock protein (HSP70) chaperone which is one of the endogenous ligands of the TLR4 also suppressed EV-induced lipid raft formation and autophagy. Pre-treatment of microglia with a selective inhibitor of αvβ3/αvβ5 integrins cilengitide inhibited EV-induced autophagy. Finally, blockage of purinergic P2X4 receptor (P2X4R) with selective inhibitor 5-BDBD also suppressed EV-induced autophagy. In conclusion, we demonstrate that EVs activate autophagy in human microglia through interaction with HSP70/TLR4, αVβ3/αVβ5, and P2X4R signaling pathways and that these effects depend on the integrity of lipid rafts. Our findings could be used to develop new therapeutic strategies targeting disease-associated microglia.

The Triggering Receptor Expressed on Myeloid Cells (TREM) family of receptors plays a crucial role in the immune response across various species. Particularly, TREM-1 and TREM-2 have been extensively studied, both in terms of their applications and their expression sites and signaling pathways. However, the same is not observed for the other family members collectively known as TREM-like-transcripts (TREML). The TREML family consists of eight receptors, with TREML1-5 identified in humans and mice, TREML-6 exclusive found in mice, TREML-7 in dogs and horses, and TREML-8 in rabbits and opossums. Despite the limited data available on the TREML members, they have been implicated in different immune and non-immune activities, which have been proposed to display both pro and anti-inflammatory activities, and to influence fundamental biological processes such as coagulation, bone and neurological development. In this review, we have compiled available information regarding the already discovered members of the family and provided foundational framework for understanding the function, localization, and therapeutic potential of all TREML members. Additionally, we hope that this review may shed light on this family of receptors, whose underlying mechanisms are still awaiting elucidation, while emphasizing the need for future studies to explore their functions and potential therapeutic application.

Nectin and nectin-like (Necl) co-receptor axis, comprised of receptors DNAM-1, TIGIT, CD96, PVRIG, and nectin/Necl ligands, is gaining prominence in immuno-oncology. Within this axis, the inhibitory receptor PVRIG recognizes Nectin-2 with high affinity, but the underlying molecular basis remains unknown. By determining the crystal structure of PVRIG in complex with Nectin-2, we identified a unique CC\' loop in PVRIG, which complements the double-lock-and-key binding mode and contributes to its high affinity for Nectin-2. The association of the corresponding charged residues in the F-strands explains the ligand selectivity of PVRIG toward Nectin-2 but not for Necl-5. Moreover, comprehensive comparisons of the binding capacities between co-receptors and ligands provide innovative insights into the intra-axis immunoregulatory mechanism. Taken together, these findings broaden our understanding of immune recognition and regulation mediated by nectin/Necl co-receptors and provide a rationale for the development of immunotherapeutic strategies targeting the nectin/Necl axis.

UNASSIGNED: 3-NP induction in rodent models has been shown to induce selective neurodegeneration in the striatum followed by the cortex (Brouillet, 2014). However, it remains unclear whether, under such a neurotoxic condition, characterized by neuroinflammation and oxidative stress, the gene expression of the immune resident protein, T-cell receptor beta subunit (TCR-β), α7 nicotinic acetylcholine receptor (α7 nAChRs), the nuclear factor kappa B (NF-κB), inflammatory cytokines (TNF-α and IL-6), and antioxidants (Cat and GpX4) get modulated on Vitamin D3 (VD) supplementation in the central nervous system.
UNASSIGNED: In the present study, real-time polymerase chain reaction (RT-PCR) was performed to study the expression of respective genes. Male C57BL/6 mice (8-12 weeks) were divided into four groups namely, Group I: Control (saline); Group II: 3-NP induction via i.p (HD); Group III: Vitamin D3 (VD) and Group IV: (HD + VD) (Manjari et al., 2022).
UNASSIGNED: On administration of 500IU/kg/day of VD, HD mice showed a significant reduction in the gene expression of the immune receptor, TCR-β subunit, nuclear factor kappa B (NF-κB), inflammatory cytokines, and key antioxidants, followed by a decrease in the acetylcholinesterase activity.
UNASSIGNED: A novel neuroprotective effect of VD in HD is demonstrated by combating the immune receptor, TCR-β gene expression, antioxidant markers, and inflammatory cytokines. In addition, HD mice on VD administration for 0-15 days showed an enhancement in cholinergic signaling with restoration in α7 nAChRs mRNA and protein expression in the striatum and cortex.

The immune system of fish possesses soluble factors, receptors, pathways and cells very similar to those of the other vertebrates\' immune system. Throughout evolutionary history, the exocrine secretions of organisms have accumulated a large reservoir of soluble factors that serve to protect organisms from microbial pathogens that could disrupt mucosal barrier homeostasis. In parallel, a diverse set of recognition molecules have been discovered that alert the organism to the presence of pathogens. The known functions of both the soluble factors and receptors mentioned above encompass critical aspects of host defense, such as pathogen binding and neutralization, opsonization, or modulation of inflammation if present. The molecules and receptors cooperate and are able to initiate the most appropriate immune response in an attempt to eliminate pathogens before host infection can begin. Furthermore, these recognition molecules, working in coordination with soluble defence factors, collaboratively erect a robust and perfectly coordinated defence system with complementary specificity, activity and tissue distribution. This intricate network constitutes an immensely effective defence mechanism for fish. In this context, the present review focuses on some of the main soluble factors and recognition molecules studied in the last decade in the skin mucosa of teleost fish. However, knowledge of these molecules is still very limited in all teleosts. Therefore, further studies are suggested throughout the review that would help to better understand the functions in which the proteins studied are involved.

Plants are exposed to a myriad of microorganisms, which can range from helpful bacteria to deadly disease-causing pathogens. The ability of plants to distinguish between helpful bacteria and dangerous pathogens allows them to continuously survive under challenging environments. The investigation of the modulation of plant immunity by beneficial microbes is critical to understand how they impact plant growth improvement and defense against invasive pathogens. Beneficial bacterial populations can produce significant impact on plant immune responses, including regulation of immune receptors activity, MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) activation, transcription factors, and reactive oxygen species (ROS) signaling. To establish themselves, beneficial bacterial populations likely reduce plant immunity. These bacteria help plants to recover from various stresses and resume a regular growth pattern after they have been established. Contrarily, pathogens prevent their colonization by releasing toxins into plant cells, which have the ability to control the local microbiota via as-yet-unidentified processes. Intense competition among microbial communities has been found to be advantageous for plant development, nutrient requirements, and activation of immune signaling. Therefore, to protect themselves from pathogens, plants may rely on the beneficial microbiota in their environment and intercommunity competition amongst microbial communities.

Plant innate immunity begins with the recognition of pathogens by plasma membrane localized pattern-recognition receptors (PRRs) and intracellular nucleotide-binding domain leucine-rich repeat containing receptors (NLRs), which lead to pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), respectively. For a long time, PTI and ETI have been regarded as two independent processes although they share multiple components and signal outputs. Increasing evidence shows an intimate link between PTI and ETI. PTI and ETI mutually potentiate each other, and this is essential for robust disease resistance during pathogen infection. An ancient class of NLRs called RNLs, so named because they carry a Resistance to Powdery Mildew 8 (RPW8)-like coiled-coil (CC) domain in the N terminus, has emerged as a key node connecting PTI and ETI. RNLs not only act as helper NLRs that signal downstream of sensor NLRs, they also directly mediate PTI signaling by associating with PRR complexes. Here, we focus on Activated Disease Resistance 1 (ADR1), a subclass of RNLs, and discuss its role and mechanism in plant immunity.

Plant intracellular immune receptors known as NLR (Nucleotide-binding Leucine-rich repeat, NB-LRR) proteins confer resistance and cause cell death upon recognition of cognate effector proteins from pathogens. Plant NLRs contain a variable N-terminal domain: a Toll/interleukin-1 receptor (TIR) domain or a coiled-coil (CC) domain or an RPW8 (Resistance to Powdery Mildew 8)-like CC (CCR) domain. TIR-NLR, CC-NLR and CCR-NLR are known as TNL, CNL and RNL, respectively. TNLs and CNLs recognize pathogen effectors to activate cell death and defense responses, thus are regarded as sensor NLRs. RNLs are required downstream of TNLs to activate cell death and defense responses, thus are regarded as helper NLRs. Previous studies show that some TNLs form tetrameric resistosome as NAD+ cleaving enzymes to transduce signal, while some CNLs form pentameric resistosome with undefined biochemical function. Two recent breakthrough studies show that activated CNL and RNL function as Ca2+ channel to cause cell death and defense responses and provide a completely new insight into the downstream signaling events of CNL and TNL pathways.