PMID- 22327491
OWN - NLM
STAT- MEDLINE
DCOM- 20130227
LR  - 20211021
IS  - 2164-554X (Electronic)
IS  - 2164-5515 (Print)
IS  - 2164-5515 (Linking)
VI  - 8
IP  - 3
DP  - 2012 Mar
TI  - Immunization with Staphylococcus aureus iron regulated surface determinant B 
      (IsdB) confers protection via Th17/IL17 pathway in a murine sepsis model.
PG  - 336-46
LID - 10.4161/hv.18946 [doi]
AB  - We have previously shown that IsdB, a conserved protein expressed by 
      Staphylococcus aureus, induces a robust antibody response which correlates with 
      protection in a murine challenge model. Here we investigate the role of cellular 
      immunity in IsdB mediated protection using lymphocyte deficient SCID mice. As 
      opposed to WT CB-17 mice the CB-17 SCID mice were not protected against a lethal 
      challenge of S. aureus after active and passive immunizations with IsdB. Adoptive 
      transfer of in vitro isolated lymphocyte subsets revealed that reconstituting 
      mice with IsdB specific CD3+ or CD4+ T-cells conferred antigen specific 
      protection while CD8(+) T-cells, CD19(+) B-cells and plasma cells 
      (CD138(high)B220(int)CD19(lo)) alone were not protective. A combination of CD3(+) 
      T-cells plus CD19(+) B-cells conferred protection in CB-17 SCID mice, whereas 
      bovine serum albumin (BSA) immune lymphocytes did not confer protection. Active 
      immunization experiments indicated that IsdB immunized Jh mice (B-cell deficient) 
      were protected against lethal challenge, while nude (T-cell deficient) mice were 
      not. In vitro assays indicated that isolated IsdB specific splenocytes from 
      immunized mice produced abundant IL-17A, much less IFN-gamma and no detectable IL-4. 
      IL-23 deficient mice were not protected from a lethal challenge by IsdB 
      vaccination, pointing to a critical role for CD4(+) Th17 in IsdB-mediated 
      vaccination. Neutralizing IL-17A, but not IL-22 in vivo significantly increased 
      mortality in IsdB immunized mice; whereas, neutralizing IFN-gamma did not alter 
      IsdB-mediated protection. These findings suggest that IL-17A producing Th17 cells 
      play an essential role in IsdB vaccine-mediated defense against invasive S. 
      aureus infection in mice.
FAU - Joshi, Amita
AU  - Joshi A
AD  - Merck Research Labs, Merck and Co. Inc., West Point, PA, USA. 
      amita_joshi@merck.com
FAU - Pancari, Greg
AU  - Pancari G
FAU - Cope, Leslie
AU  - Cope L
FAU - Bowman, Edward P
AU  - Bowman EP
FAU - Cua, Daniel
AU  - Cua D
FAU - Proctor, Richard A
AU  - Proctor RA
FAU - McNeely, Tessie
AU  - McNeely T
LA  - eng
PT  - Journal Article
DEP - 20120213
PL  - United States
TA  - Hum Vaccin Immunother
JT  - Human vaccines & immunotherapeutics
JID - 101572652
RN  - 0 (Cation Transport Proteins)
RN  - 0 (Interleukin-17)
RN  - 0 (IsdB protein, Staphylococcus aureus)
RN  - 0 (Staphylococcal Vaccines)
SB  - IM
MH  - Animals
MH  - Cation Transport Proteins/*immunology
MH  - Disease Models, Animal
MH  - Immunotherapy, Adoptive
MH  - Interleukin-17/*immunology
MH  - Mice
MH  - Mice, SCID
MH  - Sepsis/immunology/*prevention & control
MH  - Staphylococcal Infections/immunology/*prevention & control
MH  - Staphylococcal Vaccines/*administration & dosage/*immunology
MH  - T-Lymphocyte Subsets/immunology
MH  - Th17 Cells/*immunology
PMC - PMC3426080
EDAT- 2012/02/14 06:00
MHDA- 2013/02/28 06:00
PMCR- 2012/03/01
CRDT- 2012/02/14 06:00
PHST- 2012/02/14 06:00 [entrez]
PHST- 2012/02/14 06:00 [pubmed]
PHST- 2013/02/28 06:00 [medline]
PHST- 2012/03/01 00:00 [pmc-release]
AID - 18946 [pii]
AID - 2011HV0200R [pii]
AID - 10.4161/hv.18946 [doi]
PST - ppublish
SO  - Hum Vaccin Immunother. 2012 Mar;8(3):336-46. doi: 10.4161/hv.18946. Epub 2012 Feb 
      13.