Streptococcus agalactiae, often referred to as group B streptococci (GBS), is a severe pathogen that can infect humans as well as other animals, including tilapia, which is extremely popular in commercial aquaculture. This pathogen causes enormous pecuniary loss, and typical symptoms of streptococcosis—the disease caused by S. agalactiae—include abnormal behavior, exophthalmos, and meningitis, among others. Multiple studies have examined virulence factors associated with S. agalactiae infection, and vaccines were explored, including studies of subunit vaccines. Known virulence factors include capsular polysaccharide (CPS), hemolysin, Christie-Atkins-Munch-Peterson (CAMP) factor, hyaluronidase (HAase), superoxide dismutase (SOD), and serine-threonine protein kinase (STPK), and effective vaccine antigens reported to date include GapA, Sip, OCT, PGK, FbsA, and EF-Tu. In this review, I summarize findings from several studies about the etiology, pathology, virulence factors, and vaccine prospects for S. agalactiae. I end by considering which research areas are likely to yield success in the prevention and treatment of tilapia streptococcosis.

It is known that tumor growth can be influenced by the nervous system. It is not known, however, if tumors communicate directly with the central nervous system (CNS) or if such interactions may impact tumor growth. Here, we report that ventrolateral medulla (VLM) catecholaminergic (CA) neurons in the mouse brain are activated in tumor-bearing mice and the activity of these neurons significantly alter tumor growth in multiple syngeneic and spontaneous mouse tumor models. Specific ablation of VLM CA neurons by a dopamine-β-hydroxylase (DBH) promotor-activated apoptosis-promoting caspase-3 in Dbh-Cre mice as well as inhibition of these neurons by a chemogenetic method slowed tumor progression. Consistently, chemogenetic activation of VLM CA neurons promoted tumor growth. The tumor inhibition effect of VLM CA neuron ablation is mitigated in Dbh-Cre;Rag1^−/− mice, indicating that this regulatory effect is mediated by the adaptive immune system. Specific depletion of CD8⁺ T cells using an anti-CD8⁺ antibody also mitigated the tumor suppression resulting from the VLM CA neuron ablation. Finally, we showed that the VLM CA neuronal ablation had an additive antitumor effect with paclitaxel treatment. Collectively, our study uncovered the role of VLM CA neurons in the mouse brain in controlling tumor growth in the mouse body. Significance We have discovered that the ventrolateral medulla (VLM) catecholaminergic (CA) neurons, a group of neurons that control mouse stress response, are activated in tumor-bearing mice, and the neuronal activity promotes tumor growth in multiple syngeneic and spontaneous mouse tumor models. The tumor-promoting effect of these VLM CA neurons is mediated by cytotoxic T cells. These findings establish an interaction between a tumor and a group of neurons in the mouse brain that influences tumorigenesis and tumor growth by modulating adaptive immunity.

Significance: Myelin sheaths insulate the neuronal axons and speed the transmission of electrical impulses. The demyelination process occurs in many human diseases, including multiple sclerosis (MS). Using multiple mouse models of MS, we demonstrate in this study the role of MLKL, a protein known to function in a form of regulated necrosis (necroptosis), in facilitating demyelination in a necroptosis-independent manner in the central nervous system. An RIP1 kinase inhibitor was shown to block the progression of MS in an immune-induced demyelination model, and it does so at the stage after antibody generation but before breakdown of the blood–brain barrier, at a likely step of monocyte elevation. These findings provide insights into the demyelination process and potential new therapeutic agents for MS.

The danger signals that activate the related nucleotide-binding domain leucine-rich repeat pyrin domain-containing 1 (NLRP1) and caspase activation and recruitment domain-containing 8 (CARD8) inflammasomes have not been fully established. We recently reported that the oxidized form of TRX1 binds to NLRP1 and represses inflammasome activation. These findings suggested that intracellular reductive stress, which would reduce oxidized TRX1 and thereby abrogate the NLRP1-TRX1 interaction, is an NLRP1 inflammasome-activating danger signal. However, no agents that induce reductive stress were known to test this premise. Here, we identify and characterize several radical-trapping antioxidants, including JSH-23, that induce reductive stress. We show that these compounds accelerate the proteasome-mediated degradation of the repressive N-terminal fragments of both NLRP1 and CARD8, releasing the inflammasome-forming C-terminal fragments from autoinhibition. Overall, this work validates chemical probes that induce reductive stress and establishes reductive stress as a danger signal sensed by both the NLRP1 and CARD8 inflammasomes.

Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by the accumulation of cholesterol-rich lipoproteins in macrophages. How macrophages commit to proinflammatory polarization under atherosclerosis conditions is not clear. Report here that the level of a circulating protein, leucine-rich alpha-2 glycoprotein 1 (LRG1), is elevated in the atherosclerotic tissue and serum samples from patients with coronary artery disease (CAD). LRG1 stimulated macrophages to proinflammatory M1-like polarization through the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways. The LRG1 knockout mice showed significantly delayed atherogenesis progression and reduced levels of macrophage-related proinflammatory cytokines in a high-fat diet–induced Apoe ^−/− mouse atherosclerosis model. An anti-LRG1 neutralizing antibody also effectively blocked LRG1-induced macrophage M1-like polarization in vitro and conferred therapeutic benefits to animals with ApoE deficiency-induced atherosclerosis. LRG1 may therefore serve as an additional biomarker for CAD and targeting LRG1 could offer a potential therapeutic strategy for CAD patients by mitigating the proinflammatory response of macrophages.