Defining early SIV replication and dissemination dynamics following vaginal transmission

Understanding HIV transmission is critical to guide the development of prophylactic interventions to prevent infection. We used a nonhuman primate (NHP) model with a synthetic swarm of sequence-tagged variants of SIVmac239 (“SIVmac239X”) and scheduled necropsy during primary infection (days 3 to 14 after challenge) to study viral dynamics and host responses to the establishment and dissemination of infection following vaginal challenge. We demonstrate that local replication was initiated at multiple sites within the female genital tract (FGT), with each site having multiple viral variants. Local replication and spread in the FGT preceded lymphatic dissemination. Innate viral restriction factors were observed but appeared to follow viral replication and were ineffective at blocking initial viral establishment and dissemination. However, major delays were observed in time to dissemination in animals and among different viral variants within the same animal. It will be important to assess how phenotypic differences affect early viral dynamics.

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Distinct Proinflammatory Host Responses to Neisseria gonorrhoeae Infection in Immortalized Human Cervical and Vaginal Epithelial Cells

Infection and Immunity ◽

10.1128/iai.69.9.5840-5848.2001 ◽

2001 ◽

Vol 69 (9) ◽

pp. 5840-5848 ◽

Cited By ~ 111

Author(s):

Raina Nakova Fichorova ◽

Pragnya Jasvantrai Desai ◽

Frank C. Gibson ◽

Caroline Attardo Genco

Keyword(s):

Epithelial Cell ◽

Epithelial Cells ◽

Cell Lines ◽

Genital Tract ◽

Fluorescent Protein ◽

Female Genital Tract ◽

Host Responses ◽

Intercellular Adhesion Molecule ◽

Epithelial Cell Lines ◽

Female Genital

ABSTRACT In this study we utilized immortalized morphologically and functionally distinct epithelial cell lines from normal human endocervix, ectocervix, and vagina to characterize gonococcal epithelial interactions pertinent to the lower female genital tract. Piliated, but not nonpiliated, N. gonorrhoeae strain F62 variants actively invaded these epithelial cell lines, as demonstrated by an antibiotic protection assay and confocal microscopy. Invasion of these cells by green fluorescent protein-expressing gonococci was characterized by colocalization of gonococci with F actin, which were initially detected 30 min postinfection. In all three cell lines, upregulation of interleukin 8 (IL-8) and IL-6, intercellular adhesion molecule 1 (CD54), and the nonspecific cross-reacting antigen (CD66c) were detected 4 h after infection with piliated and nonpiliated gonococci. Furthermore, stimulation of all three cell lines with gonococcal whole-cell lysates resulted in a similar upregulation of IL-6 and IL-8, confirming that bacterial uptake is not essential for this response. Increased levels of IL-1 were first detected 8 h after infection with gonococci, suggesting that the earlier IL-8 and IL-6 responses were not mediated through the IL-1 signaling pathway. The IL-1 response was limited to cultures infected with piliated gonococci and was more vigorous in the endocervical epithelial cells. The ability of gonococci to stimulate distinct proinflammatory host responses in these morphologically and functionally different compartments of the lower female genital tract may contribute directly to the inflammatory signs and symptoms characteristic of disease caused by N. gonorrhoeae.

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Mucosal Immunity in the Female Genital Tract, HIV/AIDS

BioMed Research International ◽

10.1155/2014/350195 ◽

2014 ◽

Vol 2014 ◽

pp. 1-20 ◽

Cited By ~ 28

Author(s):

Juliana Reis Machado ◽

Marcos Vinícius da Silva ◽

Camila Lourencini Cavellani ◽

Marlene Antônia dos Reis ◽

Maria Luiza Gonçalves dos Reis Monteiro ◽

...

Keyword(s):

Mucosal Immunity ◽

Genital Tract ◽

Hiv Transmission ◽

Female Genital Tract ◽

Sexually Transmitted ◽

Systemic Spread ◽

Increased Risk ◽

Relationship Of ◽

Female Genital ◽

Hiv Aids

Mucosal immunity consists of innate and adaptive immune responses which can be influenced by systemic immunity. Despite having been the subject of intensive studies, it is not fully elucidated what exactly occurs after HIV contact with the female genital tract mucosa. The sexual route is the main route of HIV transmission, with an increased risk of infection in women compared to men. Several characteristics of the female genital tract make it suitable for inoculation, establishment of infection, and systemic spread of the virus, which causes local changes that may favor the development of infections by other pathogens, often called sexually transmitted diseases (STDs). The relationship of these STDs with HIV infection has been widely studied. Here we review the characteristics of mucosal immunity of the female genital tract, its alterations due to HIV/AIDS, and the characteristics of coinfections between HIV/AIDS and the most prevalent STDs.

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