Communication is key: Innate immune cells regulate host protection to helminths.

Parasitic helminth infections remain a significant global health issue and are responsible for devastating morbidity and economic hardships. During infection, helminths migrate through different host organs, which results in substantial tissue damage and the release of diverse effector molecules by both hematopoietic and non-hematopoietic cells. Thus, host protective responses to helminths must initiate mechanisms that help to promote worm clearance while simultaneously mitigating tissue injury. The specialized immunity that promotes these responses is termed type 2 inflammation and is initiated by the recruitment and activation of hematopoietic stem/progenitor cells, mast cells, basophils, eosinophils, dendritic cells, neutrophils, macrophages, myeloid-derived suppressor cells, and group 2 innate lymphoid cells. Recent work has also revealed the importance of neuron-derived signals in regulating type 2 inflammation and antihelminth immunity. These studies suggest that multiple body systems coordinate to promote optimal outcomes post-infection. In this review, we will describe the innate immune events that direct the scope and intensity of antihelminth immunity. Further, we will highlight the recent progress made in our understanding of the neuro-immune interactions that regulate these pathways and discuss the conceptual advances they promote.

Monocytes maintain central nervous system homeostasis following helminth-induced inflammation.

Neuroimmune interactions are crucial for regulating immunity and inflammation. Recent studies have revealed that the central nervous system (CNS) senses peripheral inflammation and responds by releasing molecules that limit immune cell activation, thereby promoting tolerance and tissue integrity. However, the extent to which this is a bidirectional process, and whether peripheral immune cells also promote tolerance mechanisms in the CNS remains poorly defined. Here we report that helminth-induced type 2 inflammation promotes monocyte responses in the brain that are required to inhibit excessive microglial activation and host death. Mechanistically, infection-induced monocytes express YM1 that is sufficient to inhibit tumor necrosis factor production from activated microglia. Importantly, neuroprotective monocytes persist in the brain, and infected mice are protected from subsequent lipopolysaccharide-induced neuroinflammation months after infection-induced inflammation has resolved. These studies demonstrate that infiltrating monocytes promote CNS homeostasis in response to inflammation in the periphery and demonstrate that a peripheral infection can alter the immunologic landscape of the host brain.

The Neurobiology of Modern Viral Scourges: ZIKV and COVID-19.

The interactions of viruses with the nervous system were thought to be well understood until the recent outbreaks of Zika and SARS-CoV-2. In this review, we consider these emerging pathogens, the range and mechanisms of the neurological disease in humans, and how the biomedical research enterprise has pivoted to answer questions about viral pathogenesis, immune response, and the special vulnerability of the nervous system. ZIKV stands out as the only new virus in a generation, associating with congenital brain defects, neurological manifestations of microcephaly in newborns, and radiculopathy in adults. COVID-19, the disease caused by SARS-CoV-2, has swept the planet in an unprecedented manner and is feared worldwide for its effect on the respiratory system, but recent evidence points to important neurological sequelae. These can include anosmia, vasculopathy, paresthesias, and stroke. Evidence of ZIKV and SARS-CoV-2 genetic material from neural tissue, and evidence of infection of neural cells, raises questions about how these emerging viruses produce disease, and where new therapies might emerge.

Trichinella spiralis-induced mastocytosis and erythropoiesis are simultaneously supported by a bipotent mast cell/erythrocyte precursor cell.

Anti-helminth responses require robust type 2 cytokine production that simultaneously promotes worm expulsion and initiates the resolution of helminth-induced wounds and hemorrhaging. However, how infection-induced changes in hematopoiesis contribute to these seemingly distinct processes remains unknown. Recent studies have suggested the existence of a hematopoietic progenitor with dual mast cell-erythrocyte potential. Nonetheless, whether and how these progenitors contribute to host protection during an active infection remains to be defined. Here, we employed single cell RNA-sequencing and identified that the metabolic enzyme, carbonic anhydrase (Car) 1 marks a predefined bone marrow-resident hematopoietic progenitor cell (HPC) population. Next, we generated a Car1-reporter mouse model and found that Car1-GFP positive progenitors represent bipotent mast cell/erythrocyte precursors. Finally, we show that Car1-expressing HPCs simultaneously support mast cell and erythrocyte responses during Trichinella spiralis infection. Collectively, these data suggest that mast cell/erythrocyte precursors are mobilized to promote type 2 cytokine responses and alleviate helminth-induced blood loss, developmentally linking these processes. Collectively, these studies reveal unappreciated hematopoietic events initiated by the host to combat helminth parasites and provide insight into the evolutionary pressure that may have shaped the developmental relationship between mast cells and erythrocytes.