Neutrophilia in LFA-1-deficient mice confers resistance to listeriosis: possible contribution of granulocyte-colony-stimulating factor and IL-17.
LFA-1 (CD11a/CD18) plays a crucial role in various inflammatory responses. In this study, we show that LFA-1(-/-) mice are far more resistant to Listeria monocytogenes infection than LFA-1(+/-) mice. Consistent with this, we found the following: 1) the numbers of granulocytes infiltrating the liver were markedly higher in LFA-1(-/-) mice than in LFA-1(+/-) mice, 2) increased antilisterial resistance in LFA-1(-/-) mice was abrogated by depletion of granulocytes, and 3) the numbers of granulocytes in peripheral blood, and the serum levels of both G-CSF and IL-17 were higher in LFA-1(-/-) mice than in LFA-1(+/-) mice. Neither spontaneous apoptosis nor survival of granulocytes from LFA-1(-/-) mice were affected by physiological concentrations of G-CSF. Our data suggest regulatory effects of LFA-1 on G-CSF and IL-17 secretion, and as a corollary on neutrophilia. Consequently, we conclude that increased resistance of LFA-1(-/-) mice to listeriosis is due to neutrophilia facilitating liver infiltration by granulocytes promptly after L. monocytogenes infection, although it is LFA-1 independent.
Department of Immunology, Max-Planck Institute for Infection Biology, Berlin, Germany.
Mamiko
M
Miyamoto
Masashi
M
Emoto
Yoshiko
Y
Emoto
Volker
V
Brinkmann
Izumi
I
Yoshizawa
Peter
P
Seiler
Peter
P
Aichele
Eiji
E
Kita
Stefan H E
SH
Kaufmann
D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D006098:Granulocytes / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D007113:Immunity, Innate / Q000235:genetics; D007165:Immunosuppression Therapy; D020381:Interleukin-17 / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D007958:Leukocyte Count; D007964:Leukocytosis / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008087:Listeria / Q000254:growth & development / Q000276:immunology; D008088:Listeriosis / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000098:blood supply / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D010641:Phenotype
D020381:Interleukin-17; D016169:Lymphocyte Function-Associated Antigen-1; D016179:Granulocyte Colony-Stimulating Factor; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases