Systemic and mucosal immunological responses during repeated mucosal SHIV(162P3) challenges prior to and following infection in pigtailed macaques.
Local and systemic immunological changes following vaginal HIV-1 exposures are poorly characterized and may influence susceptibility to infection. Therefore, we examined longitudinal mucosal, plasma cytokine profiles and viral-specific T-cell responses (vSTRs) before and during weekly repeated low-dose SHIV(SF162P3) viral challenges in six female pigtailed macaques, even in the absence of overt systemic infection. Following a single viral challenge, induction of several cytokines was detected consistently in cervico-vaginal lavages (CVL). With additional exposure and documented systemic infection, a hallmark of response profile was defined as peak levels in both CVL (MCP-1, MIP-1alpha, TNF-alpha, IL-1beta, IL-1RA and IL-8) and plasma cytokines (MCP-1, eotaxin and IL-1RA) in the macaques. In the periphery, vSTRs were observed within the first one or two viral challenges, but prior to the detection of systemic infection in 5/6 exposed pigtailed macaques. These findings provide valuable information regarding mucosal HIV-1 infection that may benefit microbicide research and development.
Promadej-Lanier
Nattawan
N
Laboratory Branch, Division of HIV and AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. NLanier@cdc.gov
Srinivasan
Priya
P
Curtis
Kelly
K
Adams
Debra R
DR
Kim
Caryn
C
Luo
Wei
W
Jia
Hongwei
H
Subbarao
Shambavi
S
Otten
Ron A
RA
Butera
Sal
S
D000818:Animals; D054405:Chemokine CCL3 / Q000032:analysis / Q000096:biosynthesis; D019742:Chemokines, CC / Q000032:analysis / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000096:biosynthesis / Q000097:blood; D007378:Interleukins / Q000032:analysis / Q000096:biosynthesis; D008254:Macaca nemestrina; D009092:Mucous Membrane / Q000276:immunology*; D016865:Reassortant Viruses / Q000276:immunology*; D054390:Receptors, CCR2 / Q000032:analysis / Q000096:biosynthesis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis; D014621:Vagina / Q000276:immunology
D054405:Chemokine CCL3; D019742:Chemokines, CC; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D007378:Interleukins; D054390:Receptors, CCR2; D014409:Tumor Necrosis Factor-alpha