Fig. 1. Nociceptor neurons suppress host protection against CRKP pneumonia and pneumonic sepsis.

(A) Genetic strategy for ablating TRPV1⁺ neurons in mice (left) and mouse model of CRKP lung infection (right). Control and Trpv1^DTA mice were infected with the lethal dose (10⁹ CFU per mouse) of CRKP intranasally. (B to D) Survival curve (B), clinical score (C), and core body temperature (D) of control and Trpv1^DTA mice over time. Data in (B) include Trpv1^DTA mice (n = 12) and littermate control mice (n = 12) from three independent experiments. Data in (C) and (D) are the means ± SEM and involve Trpv1^DTA mice (n = 8 to 12 mice per group) and control littermates (n = 8 to 12 mice per group). (E) Survival curve of control (n = 8) and Trpv1^DTA mice (n = 8) after intranasal challenge with heat-killed CRKP bacteria (10⁹ CFU per mouse). (F to J) CFUs recovered in blood (F), spleen (G), liver (H), whole lung (I), and BALF (J) from control and Trpv1^DTA mice at 24 hpi. Each symbol denotes a mouse [(F) to (J)]. Data in (F) to (J) are the means ± SEM and at least two independent experiments with n = 7 to 12 mice per group. Statistical analysis was done by log-rank (Mantel-Cox) test [(B) and (E)], two-way analysis of variance (ANOVA) with Sidak’s multiple comparison’s test (C), repeated measures two-way ANOVA with Sidak’s multiple comparison’s test (D), Mann-Whitney test [(F), (H), and (I)], and two-tailed unpaired t test [(G) and (J)]. Levels of significance for all statistical analyses: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. BioRender.com was used to create schematic in (A).