PMID- 11134269 OWN - NLM STAT- MEDLINE DCOM- 20010125 LR - 20181130 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 75 IP - 2 DP - 2001 Jan TI - Modulation of immunity against herpes simplex virus infection via mucosal genetic transfer of plasmid DNA encoding chemokines. PG - 569-78 AB - In this study, we examined the effects of murine chemokine DNA, as genetic adjuvants given mucosally, on the systemic and distal mucosal immune responses to plasmid DNA encoding gB of herpes simplex virus (HSV) by using the mouse model. The CC chemokines macrophage inflammatory protein 1beta (MIP-1beta) and monocyte chemotactic protein 1 (MCP-1) biased the immunity to the Th2-type pattern as judged by the ratio of immunoglobulin isotypes and interleukin-4 cytokine levels produced by CD4(+) T cells. The CXC chemokine MIP-2 and the CC chemokine MIP-1alpha, however, mounted immune responses of the Th1-type pattern, and such a response rendered recipients more resistant to HSV vaginal infection. In addition, MIP-1alpha appeared to act via the upregulation of antigen-presenting cell (APC) function and the expression of costimulatory molecules (B7-1 and B7-2), whereas MIP-2 enhanced Th1-type CD4(+) T-cell-mediated adaptive immunity by increasing gamma interferon secretion from activated NK cells. Our results emphasize the value of using the mucosal route to administer DNA modulators such as chemokines that function as adjuvants by regulating the activity of innate immunity. Our findings provide new insight into the value of CXC and CC chemokines, which act on different innate cellular components as the linkage signals between innate and adaptive immunity in mucosal DNA vaccination. FAU - Eo, S K AU - Eo SK AD - Department of Microbiology, University of Tennessee, Knoxville, Tennessee 37996, USA. FAU - Lee, S AU - Lee S FAU - Chun, S AU - Chun S FAU - Rouse, B T AU - Rouse BT LA - eng GR - R01 AI046462/AI/NIAID NIH HHS/United States GR - AI46462/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Chemokine CCL2) RN - 0 (Herpes Simplex Virus Vaccines) RN - 0 (Macrophage Inflammatory Proteins) RN - 0 (Vaccines, DNA) RN - 0 (Viral Envelope Proteins) RN - 0 (glycoprotein B, Simplexvirus) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Antigen-Presenting Cells/immunology MH - Chemokine CCL2/*genetics/immunology MH - Female MH - Herpes Simplex/*immunology/virology MH - Herpes Simplex Virus Vaccines/*immunology MH - Herpesvirus 1, Human/immunology MH - *Immunity, Mucosal MH - Immunization MH - Interferon-gamma/metabolism MH - Macrophage Inflammatory Proteins/*genetics/immunology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - *Plasmids/genetics MH - Th1 Cells/immunology MH - Vaccines, DNA MH - Vagina/immunology MH - Vaginal Diseases/immunology/prevention & control/virology MH - Viral Envelope Proteins/genetics PMC - PMC113952 EDAT- 2001/01/03 11:00 MHDA- 2001/02/28 10:01 PMCR- 2001/01/01 CRDT- 2001/01/03 11:00 PHST- 2001/01/03 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2001/01/03 11:00 [entrez] PHST- 2001/01/01 00:00 [pmc-release] AID - 1386 [pii] AID - 10.1128/JVI.75.2.569-578.2001 [doi] PST - ppublish SO - J Virol. 2001 Jan;75(2):569-78. doi: 10.1128/JVI.75.2.569-578.2001.