PMID- 16299326
OWN - NLM
STAT- MEDLINE
DCOM- 20060106
LR  - 20181113
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 73
IP  - 12
DP  - 2005 Dec
TI  - Protective immunity to the larval stages of onchocerca volvulus is dependent on 
      Toll-like receptor 4.
PG  - 8291-7
AB  - Toll-like receptor 4 (TLR4) has been shown to be important for the induction of 
      Th2-dependent immune responses in mice. Protective immunity against larval 
      Onchocerca volvulus in mice depends on the development of a Th2 immune response 
      mediated by both interleukin-4 (IL-4) and IL-5. In addition, O. volvulus contains 
      the rickettsial endosymbiont Wolbachia, which has molecules with 
      lipopolysaccharide-like activities that also signal through TLR4. We therefore 
      hypothesized that protective immunity to O. volvulus would not develop in C3H/HeJ 
      mice which have a mutation in the Tlr4 gene (TLR4 mutant), either because of a 
      decreased Th2 response to the larvae or because of the absence of a response to 
      Wolbachia. TLR4-mutant mice were immunized against O. volvulus with irradiated 
      third-stage larvae, and it was observed that Th2 responses were elevated based on 
      increased IL-5 production, total immunoglobulin E (IgE) levels, antigen-specific 
      IgG1 response, and eosinophil recruitment. Protective immunity, however, did not 
      develop in the TLR4-mutant mice. The Th1 response, as measured by gamma 
      interferon production from spleen cells, was comparable in both wild-type and 
      TLR4-mutant mice. Furthermore, antibody responses to Wolbachia were absent in 
      both wild-type and TLR4-mutant mice. Therefore, the defect in the development of 
      a protective immune response against O. volvulus in TLR4-mutant mice is not due 
      to loss of Th2 immunity or the response to Wolbachia but is due to an 
      unidentified TLR4-dependent larval killing mechanism.
FAU - Kerepesi, Laura A
AU  - Kerepesi LA
AD  - Department of Microbiology and Immunology, Thomas Jefferson University, 233 S. 
      10th St., BLSB 530, Philadelphia, PA 19107, USA.
FAU - Leon, Ofra
AU  - Leon O
FAU - Lustigman, Sarah
AU  - Lustigman S
FAU - Abraham, David
AU  - Abraham D
LA  - eng
GR  - R01 AI047189/AI/NIAID NIH HHS/United States
GR  - AI042328/AI/NIAID NIH HHS/United States
GR  - AI47189/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Helminth Proteins)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Antibody Formation
MH  - Helminth Proteins/immunology
MH  - Interferon-gamma/metabolism
MH  - Larva/immunology/ultrastructure
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Onchocerca volvulus/growth & development/*immunology/microbiology
MH  - Onchocerciasis/genetics/*immunology
MH  - Spleen/cytology
MH  - Symbiosis
MH  - Th2 Cells/immunology
MH  - Toll-Like Receptor 4/genetics/*physiology
MH  - Wolbachia/immunology/ultrastructure
PMC - PMC1307100
EDAT- 2005/11/22 09:00
MHDA- 2006/01/07 09:00
PMCR- 2005/12/01
CRDT- 2005/11/22 09:00
PHST- 2005/11/22 09:00 [pubmed]
PHST- 2006/01/07 09:00 [medline]
PHST- 2005/11/22 09:00 [entrez]
PHST- 2005/12/01 00:00 [pmc-release]
AID - 73/12/8291 [pii]
AID - 2099-04 [pii]
AID - 10.1128/IAI.73.12.8291-8297.2005 [doi]
PST - ppublish
SO  - Infect Immun. 2005 Dec;73(12):8291-7. doi: 10.1128/IAI.73.12.8291-8297.2005.