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1.  Oral and Vaginal Epithelial Cell Lines Bind and Transfer Cell-Free Infectious HIV-1 to Permissive Cells but Are Not Productively Infected 
PLoS ONE  2014;9(5):e98077.
The majority of HIV-1 infections worldwide are acquired via mucosal surfaces. However, unlike the vaginal mucosa, the issue of whether the oral mucosa can act as a portal of entry for HIV-1 infection remains controversial. To address potential differences with regard to the fate of HIV-1 after exposure to oral and vaginal epithelium, we utilized two epithelial cell lines representative of buccal (TR146) and pharyngeal (FaDu) sites of the oral cavity and compared them with a cell line derived from vaginal epithelium (A431) in order to determine (i) HIV-1 receptor gene and protein expression, (ii) whether HIV-1 genome integration into epithelial cells occurs, (iii) whether productive viral infection ensues, and (iv) whether infectious virus can be transferred to permissive cells. Using flow cytometry to measure captured virus by HIV-1 gp120 protein detection and western blot to detect HIV-1 p24 gag protein, we demonstrate that buccal, pharyngeal and vaginal epithelial cells capture CXCR4- and CCR5-utilising virus, probably via non-canonical receptors. Both oral and vaginal epithelial cells are able to transfer infectious virus to permissive cells either directly through cell-cell attachment or via transcytosis of HIV-1 across epithelial cells. However, HIV-1 integration, as measured by real-time PCR and presence of early gene mRNA transcripts and de novo protein production were not detected in either epithelial cell type. Importantly, both oral and vaginal epithelial cells were able to support integration and productive infection if HIV-1 entered via the endocytic pathway driven by VSV-G. Our data demonstrate that under normal conditions productive HIV-1 infection of epithelial cells leading to progeny virion production is unlikely, but that epithelial cells can act as mediators of systemic viral dissemination through attachment and transfer of HIV-1 to permissive cells.
doi:10.1371/journal.pone.0098077
PMCID: PMC4032250  PMID: 24857971
2.  MAPK, MKP1 and c-Fos Discriminate Candida albicans Yeast from Hyphae in Epithelial Cells 
Cell host & microbe  2010;8(3):225-235.
SUMMARY
Host mechanisms enabling discrimination between the commensal and pathogenic states of opportunistic pathogens are critical in mucosal defense and homeostasis. Here, we demonstrate that oral epithelial cells orchestrate an innate response to the human fungal pathogen Candida albicans via NF-κB and a bi-phasic MAPK response. Activation of NF-κB and the first MAPK phase, constituting c-Jun activation, is independent of morphology and due to the recognition of fungal cell wall structures. Activation of the second MAPK phase, constituting MKP1 and c-Fos activation, is dependent upon hypha-formation and fungal burdens, and correlates with proinflammatory responses. This MAPK-based discriminatory pathway may provide a mechanism for epithelial tissues to remain quiescent in the presence of low fungal burdens whilst responding specifically and strongly to damage-inducing hyphae when burdens increase. MAPK/MKP1/c-Fos activation may thus comprise a `danger response' pathway in vivo and may be critical in identifying when this normally commensal fungus has become pathogenic.
doi:10.1016/j.chom.2010.08.002
PMCID: PMC2991069  PMID: 20833374
3.  A Biphasic Innate Immune MAPK Response Discriminates between the Yeast and Hyphal Forms of Candida albicans in Epithelial Cells 
Cell Host & Microbe  2010;8(3):225-235.
Summary
Discriminating between commensal and pathogenic states of opportunistic pathogens is critical for host mucosal defense and homeostasis. The opportunistic human fungal pathogen Candida albicans is also a constituent of the normal oral flora and grows either as yeasts or hyphae. We demonstrate that oral epithelial cells orchestrate an innate response to C. albicans via NF-κB and a biphasic MAPK response. Activation of NF-κB and the first MAPK phase, constituting c-Jun activation, is independent of morphology and due to fungal cell wall recognition. Activation of the second MAPK phase, constituting MKP1 and c-Fos activation, is dependent upon hypha formation and fungal burdens and correlates with proinflammatory responses. Such biphasic response may allow epithelial tissues to remain quiescent under low fungal burdens while responding specifically and strongly to damage-inducing hyphae when burdens increase. MAPK/MKP1/c-Fos activation may represent a “danger response” pathway that is critical for identifying and responding to the pathogenic switch of commensal microbes.
Highlights
► NF-κB and MAPK control epithelial effector responses against Candida albicans ► c-Jun activation is independent of morphology and due to fungal cell wall recognition ► MAPK/MKP-1/c-Fos pathway activation is dependent on fungal hyphae and burdens ► MAPK discriminatory response may dictate C. albicans mucosal colonization in vivo
doi:10.1016/j.chom.2010.08.002
PMCID: PMC2991069  PMID: 20833374

Results 1-3 (3)