Natural killer (NK) cells develop in the bone marrow, but their in vivo stages of maturation, expansion and acquisition of receptors that guide target cell specificity are not well defined. We describe here such stages of development. We also show that developing NK cells actively proliferate at a phenotypically distinguishable immature stage after they have acquired expression of Ly49 and CD94-NKG2 receptors. These studies provide a developmental framework for NK cell maturation in vivo and suggest the possible involvement of the Ly49 and CD94-NKG2 receptors themselves in modulating expansion of NK cell populations with a given NK cell receptor repertoire.

Highlights d Adenovirus transduction of human ACE2 enables SARS-CoV-2 infection of BALB/c mice d High levels of viral RNA and infectious SARS-CoV-2 accumulate in lungs d Mice transduced with human ACE2 develop viral pneumonia after SARS-CoV-2 infection d Neutralizing mAbs protect from SARS-CoV-2-induced lung infection and inflammation

Summary The enteric pathogen Toxoplasma gondii is controlled by a vigorous innate Th1 response in the murine model. We demonstrate that following oral infection the parasite rapidly recruits inflammatory monocytes (Gr1+ Ly6C+ Ly6G− F4/80+ CD11b+ CD11c−), which establish a vital defensive perimeter within the villi of the ileum in the small intestine. Knock out mice lacking the chemokine receptor CCR2 or the ligand MCP-1, failed to recruit Gr1+ (Ly6C+) inflammatory monocytes, while dendritic cells and resident tissue macrophages remained unaltered. The selective lack of Gr1+ (Ly6C+) inflammatory monocytes resulted in an inability to control replication of the parasite, high influx of neutrophils, extensive intestinal necrosis, and rapid death. Adoptive transfer of sorted Gr1+ (Ly6C+) inflammatory monocytes demonstrated their ability to home to the ileum in infected animals and protect CCR2 −/− mice, which were otherwise highly susceptible to oral toxoplasmosis. Collectively, these findings illustrate the critical importance of inflammatory monocytes as a first line of defense in controlling intestinal pathogens.

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