Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine.
In response to enteric pathogens, the inflamed intestine produces antimicrobial proteins, a process mediated by the cytokines IL-17 and IL-22. Salmonella enterica serotype Typhimurium thrives in the inflamed intestinal environment, suggesting that the pathogen is resistant to antimicrobials it encounters in the intestinal lumen. However, the identity of these antimicrobials and corresponding bacterial resistance mechanisms remain unknown. Here, we report that enteric infection of rhesus macaques and mice with S. Typhimurium resulted in marked Il-17- and IL-22-dependent intestinal epithelial induction and luminal accumulation of lipocalin-2, an antimicrobial protein that prevents bacterial iron acquisition. Resistance to lipocalin-2, mediated by the iroBCDE iroN locus, conferred a competitive advantage to the bacterium in colonizing the inflamed intestine of wild-type but not of lipocalin-2-deficient mice. Thus, resistance to lipocalin-2 defines a specific adaptation of S. Typhimurium for growth in the inflamed intestine.
Raffatellu
Manuela
M
Department of Medical Microbiology and Immunology, University of California, Davis, CA 95616, USA.
George
Michael D
MD
Akiyama
Yuko
Y
Hornsby
Michael J
MJ
Nuccio
Sean-Paul
SP
Paixao
Tatiane A
TA
Butler
Brian P
BP
Chu
Hiutung
H
Santos
Renato L
RL
Berger
Thorsten
T
Mak
Tak W
TW
Tsolis
Renée M
RM
Bevins
Charles L
CL
Solnick
Jay V
JV
Dandekar
Satya
S
Bäumler
Andreas J
AJ
D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D054834:Lipocalins / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D051379:Mice; D008810:Mice, Inbred C57BL; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000276:immunology / Q000502:physiology*; D017262:Siderophores / Q000276:immunology; D000097043:Interleukin-22
D020381:Interleukin-17; D007378:Interleukins; D054834:Lipocalins; D017262:Siderophores; D000097043:Interleukin-22