DOCK2 confers immunity and intestinal colonization resistance to Citrobacter rodentium infection.
Food poisoning is one of the leading causes of morbidity and mortality in the world. Citrobacter rodentium is an enteric pathogen which attaches itself to enterocytes and induces attachment and effacing (A/E) lesions. The ability of the bacterium to cause infection requires subversion of the host actin cytoskeleton. Rac-dependent actin polymerization is activated by a guanine nucleotide exchange factor known as Dedicator of cytokinesis 2 (DOCK2). However, the role of DOCK2 in infectious disease is largely unexplored. Here, we found that mice lacking DOCK2 were susceptible to C. rodentium infection. These mice harbored increased levels of C. rodentium bacteria, showed more pronounced weight loss and inflammation-associated pathology, and were prone to bacterial dissemination to the systemic organs compared with wild-type mice. We found that mice lacking DOCK2 were more susceptible to C. rodentium attachment to intestinal epithelial cells. Therefore, our results underscored an important role of DOCK2 for gastrointestinal immunity to C. rodentium infection.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Zhiping
Z
Liu
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Si Ming
SM
Man
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.|Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Qifan
Q
Zhu
Animal Resources Center and the Veterinary Pathology Core, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Peter
P
Vogel
Cell and Tissue Imaging Center, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Sharon
S
Frase
Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
Yoshinori
Y
Fukui
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Thirumala-Devi
TD
Kanneganti
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D044082:Citrobacter rodentium / Q000502:physiology*; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D060467:Disease Resistance / Q000276:immunology*; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D020690:GTPase-Activating Proteins / Q000172:deficiency / Q000235:genetics*; D020662:Guanine Nucleotide Exchange Factors; D007410:Intestinal Diseases / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000166:cytology / Q000276:immunology
D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; C471356:DOCK2 protein, mouse; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors