IL-17 and γδ T-lymphocytes play a critical role in innate immunity against Nocardia asteroides GUH-2.
The early host response during pulmonary nocardiosis is highly dependent on neutrophils and the successful clearance of bacteria in tissue. The data presented in this study showed that IL-17 mediated the neutrophil response following intranasal inoculation with Nocardia asteroides strain GUH-2. Flow cytometry revealed that neutrophil levels in C57BL/6 mice were increased by day 1 post inoculation and remained elevated until day 3, during which time the majority of bacterial clearance occurred. Intracellular cytokine staining for IL-17 showed a 3.5- to 5-fold increase in IL-17 producing T-lymphocytes that were predominately comprised by CD4(-)CD8(-) γδ T-lymphocytes. The importance of IL-17 and γδ T-cells was determined by the in vivo administration of antibody, capable of blocking IL-17 binding or TCR δ, respectively. Neutralization of either IL-17 or γδ T-cells in Nocardia treated mice resulted in attenuated neutrophil infiltration. Paralleling this impaired neutrophil recruitment, nearly a 10-fold increase in bacterial burden was observed in both anti-IL-17 and anti-TCR δ treated animals. Together, these data indicate a protective role for IL-17 and suggest that IL-17 producing γδ T-lymphocytes contribute to neutrophil infiltration during pulmonary nocardiosis.
Respiratory Disease Unit, California National Primate Research Center (CNPRC), University of California, Davis, CA 95616, USA. sstam@ucdavis.edu
Stanley
S
Tam
Saipiroon
S
Maksaereekul
Dallas M
DM
Hyde
Ivan
I
Godinez
Blaine L
BL
Beaman
D000818:Animals; D005260:Female; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D009617:Nocardia Infections / Q000276:immunology* / Q000382:microbiology; D009616:Nocardia asteroides / Q000254:growth & development / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta