BackgroundToll-like receptors (TLR) 7 and 8 are important in single-stranded viral RNA recognition and may play a role in HIV infection and disease progression. We analyzed TLR7/8 expression and signaling in monocytes from HIV-infected and uninfected subjects to investigate a pathway with new potential for the suppression of HIV replication.MethodsEighty-one HIV-infected and uninfected subjects from Liaoning and Henan provinces in China participated in this study. Monocytes were isolated from subjects' peripheral blood mononuclear cells by magnetic bead selection. TLR7 and TLR8 mRNA was measured using quantitative real-time reverse transcriptase PCR. R-848 (resiquimod) was used as a ligand for TLR7 and TLR8 in order to 1) assess TLR7/8-mediated monocyte responsiveness as indicated by IL-12 p40 and TNF-α secretion and 2) to examine HIV replication in cultured monocytes in the presence of R-848.ResultsWe found that expression of TLR7/8 mRNA in peripheral blood monocytes decreased with disease progression. TLR7 expression was decreased with stimulation with the TLR7/8 agonist, R-848, in vitro, whereas TLR8 expression was unaffected. Following R-848 stimulation, monocytes from HIV-infected subjects produced significantly less TNF-α than those from uninfected subjects, but trended towards greater production of IL-12 than stimulated monocytes from uninfected subjects. R-848 stimulation also suppressed HIV replication in cultured monocytes.ConclusionsOur study provides evidence that the TLR7 and TLR8 triggering can suppress HIV replication in monocytes and lead to postpone HIV disease progression, thereby offering novel targets for immunomodulatory therapy.

Orbital apex syndrome is a life-threatening disease that is very rarely caused by anaerobic bacterial infections. In particular, Peptostreptococcus stomatis, a newly discovered species of Peptostreptococcus species, which is commonly thought to be associated with the development of colorectal cancer (CRC) in patients and oral squamous cell carcinoma (OSCC). However, there is no report that other site infections and bacteremia was caused by this organism. We firstly herein report a case of P.stomatis bacteremia in a 63-year-old woman who was diagnosed with left orbital apex syndrome and cellulitis of both eyelids originated from a dental reparation. This report illustrates the importance of using traditional methods and experience for identification when MALDI-TOF MS failed, which still facilitates the timely selection of appropriate antibiotics for treatment, thus achieving a favorable outcome.

Abstract. The identification of broadly cross-reactive neutralizing (BCN) antibodies is essential for the development of a more universally effective vaccine for human immunodeficiency virus (HIV). In this study, CRF07_BC serum was analyzed for cross-clade antibody reactivity and neutralization. A total of 117 HIV-1 sera (CRF07_BC) were screened for their capacity to neutralize three primary HIV-1 isolates. A total of 18 out of 117 sera cross-neutralized all three viruses, and were tested along with eight randomly selected non-BCN sera against seven primary HIV-1 isolates and two laboratory strains that represented different clades and tropisms. BCN sera neutralized eight or all nine of these primary isolates. Non-BCN sera did not display any broadly cross-reactive neutralizing responses. BCN sera neutralized with higher frequency and geometric mean titers compared to non-BCN sera. Sera from asymptomatic individuals on average neutralized a significantly greater number of the three key isolates than sera from symptomatic individuals. Our data indicate that the three HIV-1 isolated strains are sufficient to screen broad cross-neutralizing sera, and that BCN responses may contribute to protection from infection and disease progression. The neutralizing antibody response demonstrated extensive cross-neutralization, suggesting that neutralizing antibodies induced by vaccines will have a relatively low epitope diversity to overcome in patients infected with HIV-1 B'/C recombinant (CRF07_BC).