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1.  The Role of MyD88 Signaling in Heterosubtypic Influenza A Virus Infections 
Virus research  2012;171(1):216-221.
A mouse model of heterosubtypic influenza A virus infections was used to determine the role of MyD88 signaling in CD4+ T-cell, CD8+ T-cell, and IgG immune responses. We found that MyD88 signaling played an important role in anti-influenza A virus heterosubtypic lung and spleen CD4+ T-cell, and spleen CD8+ T-cell, immune responses. MyD88 dependent signaling was important for T-helper 1 cytokine production in anti-influenza A virus lung and spleen heterosubtypic CD4+ T-cells, but not for their frequencies. Toll-like receptor 7 dependent signaling played a partial role in anti-influenza A virus lung heterosubtypic CD4+ T-helper 1 responses and anti-influenza A virus heterosubtypic IgG2c antibody levels. Our results have important implications for the generation of effective universal influenza vaccines.
doi:10.1016/j.virusres.2012.12.004
PMCID: PMC3557579  PMID: 23238076
Influenza A virus; heterosubtypic; MyD88; TLR7; T-cell; antibody
2.  Plasmacytoid dendritic cell interferon-α production to R-848 stimulation is decreased in male infants 
BMC Immunology  2012;13:35.
Background
Sex differences in response to microbial infections, especially viral ones, may be associated with Toll-like receptor (TLR)-mediated responses by plasmacytoid dendritic cells (pDCs).
Results
In this study, we identified sex differences in human infant pDC interferon-α production following challenge with the TLR7/8 agonist R-848. Male pDC responses were significantly lower than those of females during early infancy. This difference may be attributed to the androgen surge experienced by males during the early infancy period. Pretreatment of human pDCs with dihydrotestosterone produced a significant reduction in interferon-α production following R-848 challenge.
Conclusions
Androgen-mediated regulation of pDC TLR7-driven innate immune responses may contribute to the observed sex differences in response to infections during early infancy.
doi:10.1186/1471-2172-13-35
PMCID: PMC3411434  PMID: 22769054
pDC; IFN-α; TNF-α; Infant; TLR7
3.  The Combination of Early and Rapid Type I IFN, IL-1α, and IL-1β Production Are Essential Mediators of RNA-Like Adjuvant Driven CD4+ Th1 Responses 
PLoS ONE  2011;6(12):e29412.
There is a growing need for novel vaccine adjuvants that can provide safe and potent T-helper type 1 (Th1) activity. RNA-like immune response modifiers (IRMs) are candidate T-cell adjuvants that skew acquired immune responses towards a Th1 phenotype. We set out to delineate the essential signaling pathways by which the RNA-like IRMs, resiquimod (R-848) and polyinosinic:polycytidylic acid (poly I:C), augment CD4+ T-helper 1 (Th1) responses. Highly purified murine conventional dendritic cells (cDCs) and conventional CD4+ T-cells were co-cultured in allogeneic and MHC congenic mixed leukocyte reactions. The activation of CD4+ Th1 cells was examined utilizing cells from mice deficient in specific RNA-sensing pattern recognition receptors and signaling mediators. R-848 and poly I:C stimulation of Type I interferon production and signaling in cDCs was essential but not sufficient for driving CD4+ Th1 responses. The early and rapid production of IL-1α and IL-1β was equally critical for the optimal activation of Th1 CD4+ T-cells. R-848 activation of Toll-like receptor 7/MyD88-dependent signaling in cDCs led to a rapid upregulation of pro-IL-1α and pro-IL-1β production compared to poly I:C activation of MyD88-independent signaling pathways. The in vitro data show that CD4+ T-cell adjuvant activity of RNA-like IRMs is mediated by a critical combination of early and rapid Type I interferon, IL-1α and IL-1β production. These results provide important insights into the key signaling pathways responsible for RNA-like IRM CD4+ Th1 activation. A better understanding of the critical signaling pathways by which RNA-like IRMs stimulate CD4+ Th1 responses is relevant to the rational design of improved vaccine adjuvants.
doi:10.1371/journal.pone.0029412
PMCID: PMC3242790  PMID: 22206014

Results 1-3 (3)