scholarly journals Expression of MIP-1α (CCL3) by a Recombinant Rabies Virus Enhances Its Immunogenicity by Inducing Innate Immunity and Recruiting Dendritic Cells and B Cells

2010 ◽  
Vol 84 (18) ◽  
pp. 9642-9648 ◽  
Author(s):  
Ling Zhao ◽  
Harufusa Toriumi ◽  
Hualei Wang ◽  
Yi Kuang ◽  
Xiaofeng Guo ◽  
...  

ABSTRACT Previously, we showed that overexpression of MIP-1α in mouse brain further decreased rabies virus (RABV) pathogenicity (L. Zhao, H. Toriumi, Y. Kuang, H. Chen, and Z. F. Fu, J. Virol., 83:11808-11818, 2009). In the present study, the immunogenicity of recombinant RABV expressing MIP-1α (rHEP-MIP1α) was determined. It was found that intramuscular immunization of BALB/c mice with rHEP-MIP1α resulted in a higher level of expression of MIP-1α at the site of inoculation, increased recruitment of dendritic cells (DCs) and mature B cells into the draining lymph nodes and the peripheral blood, and higher virus-neutralizing antibody titers than immunization with the parent rHEP and recombinant RABVs expressing RANTES (CCL5) or IP-10 (CXCL10). Our data thus demonstrate that expression of MIP-1α not only reduces viral pathogenicity but also enhances immunogenicity by recruiting DCs and B cells to the site of immunization, the lymph nodes, and the blood.

PEDIATRICS ◽  
1949 ◽  
Vol 4 (4) ◽  
pp. 443-453
Author(s):  
ALBERT B. SABIN

An antigen prepared from toxoplasma-infected chorioallantoic membranes, improved by centrifugation at 13,000 r.p.m. for one hour which removed a nonspecific component capable of fixing complement with certain normal sera, proved to be the preparation of choice for toxoplasmic CF tests. Though it was possible to prepare an antigen of similar potency from mouse brain, the yield from one egg is at least 10 times more than from one mouse. The peritoneal exudate of mice freed of Toxoplasma and cells contains eight times as much antigen per unit volume as a 20% extract of mouse brain or chorioallantoic membranes, but its anticomplementary properties, which cannot be removed by high speed centrifugation, can be eliminated only by extensive dilution. The highly centrifuged and diluted peritoneal exudate, however, still contains a component which fixes complement with certain normal human sera. Sixteen children, aged 5 weeks to 11 years, with clinically recognized congenital toxoplasmosis and 17 mothers, with inapparent or clinically unrecognized infection except for having given birth to children with proved toxoplasmosis, were investigated for the presence and persistence of CF antibodies. With the improved antigen and the standardized method that was used, even titers of 1:2 and 1:4 were significant and invariably associated with toxoplasmic neutralizing antibody. The sera of all 17 mothers gave positive CF tests with titers ranging from 1:4 to 1:64, the higher titers predominating during the first two years after the delivery of the infected child. The sera of 14 of the 16 children (87.5%) with clinical evidence of congenital toxoplasmosis, confirmed by neutralization tests, gave positive CF tests with titers ranging from 1:2 to 1:128, the higher titers again predominating during the first two years after birth. One of the negative results, in a 5 week old child with active infection who died three days after the serum was obtained, was associated with a high (1:4,096) dye test titer for neutralizing antibody in its own serum, and a similar dye test titer (1:4,096) and a CF titer of 1:32 in the serum of its mother. The other negative result, in a 7 year old child with a dye test titer of 1:16, is believed to represent an instance of disappearance of CF antibody after an interval of seven years. Not one serum obtained from 24 children with congenital ocular or neurologic disturbances or both, not due to toxoplasmosis, gave a positive CF test with the toxoplasmic antigen; however, among 20 of their mothers, there were four sera with titers of 1:2, 1:2, 1:8 and 1:16. Toxoplasmic CF antibody can persist for at least six years, and in some instances even longer, in individuals with clinically recognized as well as inapparent or clinically unrecognized infections. Since at least seven of the mothers, who gave birth to children with congenital toxoplasmosis, subsequently gave birth to normal children at a time when the CF antibody titers in some of them were still high (32, 32, 32, 16, 8, 4, 4), it is clear that this antibody can persist in individuals in whom the infection has been eradicated or suppressed sufficiently to prevent its congenital transmission.


1998 ◽  
Vol 31 (10) ◽  
pp. 1275-1280 ◽  
Author(s):  
C.R. Zanetti ◽  
C.A. Consales ◽  
A.C. Rodrigues-da-Silva ◽  
Y.K. Toyoshima ◽  
O.A.C. Pereira

2021 ◽  
Vol 118 (3) ◽  
pp. e2021364118
Author(s):  
Hannah L. Miller ◽  
Prabhakar Sairam Andhey ◽  
Melissa K. Swiecki ◽  
Bruce A. Rosa ◽  
Konstantin Zaitsev ◽  
...  

Plasmacytoid dendritic cells (pDCs) specialize in the production of type I IFN (IFN-I). pDCs can be depleted in vivo by injecting diphtheria toxin (DT) in a mouse in which pDCs express a diphtheria toxin receptor (DTR) transgene driven by the human CLEC4C promoter. This promoter is enriched for binding sites for TCF4, a transcription factor that promotes pDC differentiation and expression of pDC markers, including CLEC4C. Here, we found that injection of DT in CLEC4C-DTR+ mice markedly augmented Th2-dependent skin inflammation in a model of contact hypersensitivity (CHS) induced by the hapten fluorescein isothiocyanate. Unexpectedly, this biased Th2 response was independent of reduced IFN-I accompanying pDC depletion. In fact, DT treatment altered the representation of conventional dendritic cells (cDCs) in the skin-draining lymph nodes during the sensitization phase of CHS; there were fewer Th1-priming CD326+ CD103+ cDC1 and more Th2-priming CD11b+ cDC2. Single-cell RNA-sequencing of CLEC4C-DTR+ cDCs revealed that CD326+ DCs, like pDCs, expressed DTR and were depleted together with pDCs by DT treatment. Since CD326+ DCs did not express Tcf4, DTR expression might be driven by yet-undefined transcription factors activating the CLEC4C promoter. These results demonstrate that altered DC representation in the skin-draining lymph nodes during sensitization to allergens can cause Th2-driven CHS.


2019 ◽  
Vol 114 ◽  
pp. 172-178 ◽  
Author(s):  
Mohsen Arabpour ◽  
Reza Rasolmali ◽  
Abdoul-Rasoul Talei ◽  
Fereshteh Mehdipour ◽  
Abbas Ghaderi

2009 ◽  
Vol 131 ◽  
pp. S19
Author(s):  
Sally Kent ◽  
Elizabeth Bradshaw ◽  
Qing Han ◽  
Navin Varadarajan ◽  
Allison Greer ◽  
...  

2007 ◽  
Vol 36 (3) ◽  
pp. 360-367 ◽  
Author(s):  
Alexander Faith ◽  
Emma Peek ◽  
Joanne McDonald ◽  
Zoe Urry ◽  
David F. Richards ◽  
...  

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