Cathelicidin Antimicrobial Peptide Expression Is Not Induced or Required for Bacterial Clearance during Salmonella enterica Infection

Salmonella enterica serovar Typhimurium is able to resist antimicrobial peptide killing by induction of the PhoP-PhoQ and PmrA-PmrB two-component systems and the lipopolysaccharide (LPS) modifications they mediate. Murine cathelin-related antimicrobial peptide (CRAMP) has been reported to inhibit S. Typhimurium growth in vitro and in vivo. We hypothesize that infection of humanmonocyte-derived macrophages (MDMs) with Salmonella enterica serovar Typhi and S. Typhimurium will induce human cathelicidin antimicrobial peptide (CAMP) production, and exposure to LL-37 (processed, active form of CAMP/ hCAP18) will lead to upregulation of PmrAB-mediated LPS modifications and increased survival in vivo. Unlike in mouse mac-rophages, in which CRAMP is upregulated during infection, camp gene expression was not induced in humanMDMs infected with S. Typhi or S. Typhimurium. Upon infection, intracellular levels ofphoPQ,pmrAB, and PhoPc S. Typhi decreased over time but were not further inhibited by the vitamin D3-induced increase in camp expression. MDMs infected with wild-type (WT) S. Typhi or S. Typhimurium released similar levels of proinflammatory cytokines; however, the LPSmodificationmutant strains dramatically differed inMDM-elicited cytokine levels. Overall, these findings indicate that camp is not induced during Salmo-nella infection of MDMs nor is key to Salmonella intracellular clearance. However, the cytokine responses fromMDMs infected withWT or LPSmodificationmutant strains differ significantly, indicating a role for LPSmodifications in altering the host in-flammatory response. Our findings also suggest that S. Typhi and S. Typhimurium elicit different proinflammatory responses fromMDMs, despite being capable of adding similar modifications to their LPS structures