LAUSR

In the current issue of Journal of Leukocyte Biology, Kugadas et al.1 examined a murine model of Pseudomonas aeruginosa infection of the cornea where the bacteria produce an exo-polysaccharide biofilm. These investigators demonstrated that outbred Swiss-Webster (SW) mice are highly resistant to infection compared with C57BL/6N mice, and that neutrophils from SW mice more effectively kill P. aeruginosa in vitro than C57BL/6N neutrophils. Bacterial biofilms aredefined as a community of bacteria embedded in a polymeric extracellularmatrix producedby the bacteria, andwhich are strongly adherent to biological and other surfaces. Bacteria in biofilm differ metabolically from individual bacterial clusters, and the biofilm protects bacteria from antimicrobial agents, physical and biological stresses, and the host response. The authors demonstrate biofilm formation on the corneas of infected C57BL/6N mice by intravital microscopy and show that infiltrating neutrophils are unable to penetrate the biofilm and thereby cannot control the infection. When they performed proteomic analysis of bone marrow neutrophils from naïve and P. aeruginosa infected SW and C57BL/6 mice, Kugadas et al. found 695 proteins in higher abundance in SW compared with C57BL/6 neutrophils, including α-mannosidase (Man2b1 and Man2b1; Fig. 1). They then treated infected C57BL/6 mice topically with α-mannosidase, which digested the biofilm and allowed neutrophils to kill the bacteria. In a prior study, the same investigators reported that SWmicemaintained under germ-free conditions were more susceptible to infection and showed that intrinsic resistance of outbred SW mice to P. aeruginosa corneal infections is due to the microbiome of the ocular surface (primarily the conjunctiva) and the gut.2 In support of these findings with outbred mice, another recent study in Nature showed that T cells from outbred mice (purchased from pet stores or captured from barns) had immune signatures that resembled mature human T cells, whereas T cells from inbred mice were more closely related to neonatal human cells.3 That study also demonstrated that co-housing inbred together with outbred mice resulted in development ofmorematureT cells in inbredmice, and that co-housed inbred mice were more resistant to infection than non-cohoused inbred mice. Thus, outbred strains of mice with an appropriate 0