Prevalence and Associated Factors of Unprotected Anal Intercourse with Regular Male Sex Partners among HIV Negative Men Who Have Sex with Men in China: A Cross-Sectional Survey

The HIV prevalence and incidence among men who have sex with men (MSM) in China are high. Unprotected anal intercourse (UAI) with a regular male sex partner (RP), a significant predictor of HIV sero-conversion, was high yet under-emphasized among MSM having RP (MSMRP). The present cross-sectional survey interviewed 307 HIV negative MSMRP recruited through convenient sampling from multiple sources, including venue-based outreaching, online recruitment, and referrals made by peers, in Beijing and Chengdu, China. Among MSMRP, the prevalence of UAI with RP in the last three months was 52.4%. The results of the multivariate analysis showed that trust and intimacy within the relationship with RP and presence of clinical depression symptoms were positively associated with UAI with RP in the last three months. Other associated scalar factors derived from the Theory of Planned Behavior were related to perceptions on condom use, including positive attitudes toward condom use (a negative association), subjective norm of the perception that MSM do not usually use condoms during anal intercourse with RP (a positive association), perceived behavioral control over condom use with RP (a negative association), and behavioral intention to use condoms with RP in the coming three months (a negative association). It is seen that MSMRP were at high risk of HIV/STD transmission. The associated factors hence involved those related to perceptions about condom use, mental health, and interpersonal relationship. Future interventions should take these multi-dimensional factors into account. In particular, future research to test the efficacy of couple-based interventions that include mental health elements needs to be conducted, as trust and intimacy within the relationship were associated with UAI among MSMRP, and mental health problems may exist for both the MSMRP and their RP.     

IL-22 and IDO1 Affect Immunity and Tolerance to Murine and Human Vaginal Candidiasis

The ability to tolerate Candida albicans, a human commensal of the gastrointestinal tract and vagina, implicates that host defense mechanisms of resistance and tolerance cooperate to limit fungal burden and inflammation at the different body sites. We evaluated resistance and tolerance to the fungus in experimental and human vulvovaginal candidiasis (VVC) as well as in recurrent VVC (RVVC). Resistance and tolerance mechanisms were both activated in murine VVC, involving IL-22 and IL-10-producing regulatory T cells, respectively, with a major contribution by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). IDO1 was responsible for the production of tolerogenic kynurenines, such that replacement therapy with kynurenines restored immunoprotection to VVC. In humans, two functional genetic variants in IL22 and IDO1 genes were found to be associated with heightened resistance to RVVC, and they correlated with increased local expression of IL-22, IDO1 and kynurenines. Thus, IL-22 and IDO1 are crucial in balancing resistance with tolerance to Candida, their deficiencies are risk factors for RVVC, and targeting tolerance via therapeutic kynurenines may benefit patients with RVVC.     

The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity

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Effect of Age and Sex on the Acquisition of Immunity to Toxoplasmosis in Cats*

SYNOPSIS. The effects of age and sex of the cat on oocyst shedding, multiplication of Toxoplasma gondii in tissues of cats, and acquisition of immunity were investigated after oral inoculation of cats with Toxoplasma cysts. Twenty-five cats varying in age from 1 week to 39 months were killed 7-97 days after inoculation with T. gondii. Homogenates of brain, heart, mesenteric lymph nodes, retina, and blood from these cats were inoculated into mice to test for Toxoplasma infectivity. Toxoplasma was isolated more frequently and in higher titers in mice receiving inocula from cats of the youngest age group (1 week old). Toxoplasma gondii was isolated from tissues of only 2 of 21 cats older than 2 months (at the time of inoculation), although all of the animals shed oocysts within 1 week after ingesting the parasites. The number of oocysts shed varied among littermates of the same sex and between sexes. Generally, cats younger than 12 months shed more oocysts than older cats. The number of oocysts shed by older cats varied considerably; males generally shed more oocysts than the females. However, the numbers of cats examined were too small for statistical comparison. Nevertheless, the observations suggest that cats older than 12 months should not be used in experiments where numbers of oocysts shed is critical.     

High Tolerance to Salinity and Herbivory Stresses May Explain the Expansion of Ipomoea Cairica to Salt Marshes

Background

Invasive plants are often confronted with heterogeneous environments and various stress factors during their secondary phase of invasion into more stressful habitats. A high tolerance to stress factors may allow exotics to successfully invade stressful environments. Ipomoea cairica, a vigorous invader in South China, has recently been expanding into salt marshes.

Methodology/Principal Findings

To examine why this liana species is able to invade a stressful saline environment, we utilized I. cairica and 3 non-invasive species for a greenhouse experiment. The plants were subjected to three levels of salinity (i.e., watered with 0, 4 and 8 g L⁻¹ NaCl solutions) and simulated herbivory (0, 25 and 50% of the leaf area excised) treatments. The relative growth rate (RGR) of I. cairica was significantly higher than the RGR of non-invasive species under both stress treatments. The growth performance of I. cairica was not significantly affected by either stress factor, while that of the non-invasive species was significantly inhibited. The leaf condensed tannin content was generally lower in I. cairica than in the non-invasive I. triloba and Paederia foetida. Ipomoea cairica exhibited a relatively low resistance to herbivory, however, its tolerance to stress factors was significantly higher than either of the non-invasive species.

Conclusions/Significance

This is the first study examining the expansion of I. cairica to salt marshes in its introduced range. Our results suggest that the high tolerance of I. cairica to key stress factors (e.g., salinity and herbivory) contributes to its invasion into salt marshes. For I. cairica, a trade-off in resource reallocation may allow increased resources to be allocated to tolerance and growth. This may contribute to a secondary invasion into stressful habitats. Finally, we suggest that I. cairica could spread further and successfully occupy salt marshes, and countermeasures based on herbivory could be ineffective for controlling this invasion.     

Distinct Innate Immunity Pathways to Activation and Tolerance in Subgroups of Chronic Lymphocytic Leukemia with Distinct Immunoglobulin Receptors

Subgroups of patients with chronic lymphocytic leukemia (CLL) have distinct expression profiles of Toll-like receptor (TLR) pathway–associated genes. To test the hypothesis that signaling through innate immunity receptors may influence the behavior of the malignant clone, we investigated the functional response triggered by the stimulation of TLRs and NOD2 in 67 CLL cases assigned to different subgroups on the basis of immunoglobulin heavy variable (IGHV ) gene usage, IGHV gene mutational status or B-cell receptor (BcR) stereotypy. Differences in the induction of costimulatory molecules and/or apoptosis were observed in mutated versus unmutated CLL. Different responses were also identified in subsets with stereotyped BcRs, underscoring the idea that “subset-biased” innate immunity responses may occur independently of mutational status. Additionally, differential modulation of kinase activities was induced by TLR stimulation of different CLL subgroups, revealing a TLR7-tolerant state for cases belonging to stereotyped subset #4. The distinct patterns of TLR/NOD2 functional activity in cells from CLL subgroups defined by the molecular features of the clonotypic BcRs might prove relevant for elucidating the immune mechanisms underlying CLL natural history and for defining subgroups of patients who might benefit from treatment with specific TLR ligands.     

Heterosexual men and women both show a hypothalamic response to the chemo-signal androstadienone

The odorous steroid compound 4,16-androstadien-3-one (androstadienone), found in axillary sweat, was previously reported to evoke hypothalamic activation in heterosexual women, but not in heterosexual men. However, subjects were exposed to the pure crystalline form of androstadienone, which raised the question whether the observed hypothalamic response is physiologically relevant. Therefore, in the present study, we asked whether sexually dimorphic hypothalamic responses could be measured when subjects were exposed to lower, more physiologically relevant concentrations of androstadienone. A total of 21 women and 16 men, all heterosexual, participated in our functional magnetic resonance imaging study (fMRI). Three different concentrations of androstadienone diluted in propylene glycol (10 mM "high," 0.1 mM "medium" and 0.001 mM "low") were delivered to the subjects' nostrils using a computer-controlled stimulator. When exposed to the "high" androstadienone concentration, women showed stronger hypothalamic activation than men. By contrast, men showed more hypothalamic activation when exposed to the "medium" androstadienone concentrations in comparison to women. Thus, we replicated that smelling the chemo-signal androstadienone elicits a hypothalamic activation. However, this effect does not seem to be gender-specific, because androstadienone activated the hypothalamus in both men and women, suggesting that androstadienone exerts specific effects in heterosexual individuals of both sexes.     

The Contribution of Emotional Partners to Sexual Risk Taking and Violence among Female Sex Workers in Mombasa,Kenya: A Cohort Study

Objectives

To assess sexual risk-taking of female sex workers (FSWs) with emotional partners (boyfriends and husbands), compared to regular and casual clients. Experiences of violence and the degree of relationship control that FSWs have with emotional partners are also described.

Design

Cohort study with quarterly follow-up visit over 12-months.

Methods

Four hundred HIV-uninfected FSWs older than 16 years were recruited from their homes and guesthouses in Mombasa, Kenya. A structured questionnaire assessed participant characteristics and study outcomes at each visit, and women received risk-reduction counselling, male and female condoms, and HIV testing.

Results

Four or more unprotected sex acts in the past week were reported by 21.3% of women during sex with emotional partners, compared to 5.8% with regular and 4.8% with casual clients (P<0.001). Total number of unprotected sex acts per week was 5–6-fold higher with emotional partners (603 acts with 259 partners) than with regular or casual clients (125 acts with 456, and 98 acts with 632 clients, respectively; P<0.001). Mostly, perceptions of “trust” underscored unprotected sex with emotional partners. Low control over these relationships, common to many women (36.9%), was linked with higher partner numbers, inconsistent condom use, and being physically forced to have sex by their emotional partners. Half experienced sexual or physical violence in the past year, similarly associated with partner numbers and inconsistent condom use.

Conclusions

High-risk sexual behaviour, low control and frequent violence in relationships with emotional partners heighten FSWs'' vulnerability and high HIV risk, requiring targeted interventions that also encompass emotional partners.     

Immunity to tuberculosis: a delicate balance between protection and pathology

The currently used tuberculosis (TB) vaccine (Bacillus Calmette-Guérin) does not consistently prevent pulmonary infection. Novel vaccine strategies require an in-depth characterization of the cellular and molecular mechanisms of antituberculous protection. This review summarizes relevant data obtained in animal models of TB infection. In mycobacterial infections, immunologically mediated protection is intrinsically associated with tissue damage in the form of granuloma formation. The implications of this finding for future vaccine design and evaluation are discussed.     

Modulation of Cytokine Secretion Allows CD4 T Cells Secreting IL-10 and IL-17 to Simultaneously Participate in Maintaining Tolerance and Immunity

CD4 T cells secreting IL-10 or IL-17 are frequent at mucosal sites, where their equilibrium is important for simultaneously maintaining tolerance and immunity to the resident microbiota. The mode of action of these cells, however, is as yet incompletely understood. In this study, we have combined ex vivo analysis of CD4 T cells producing IL-10 or/and IL-17 with assessment of clonal populations isolated ex vivo using a cytokine catch assay. We found that circulating CD4 T cells secreting IL-10 or/and IL-17 ex vivo include both conventional FOXP3^- CD4 T cells and FOXP3⁺ Helios^- Treg. Upon assessment of clonal populations derived from single ex vivo isolated cytokine secreting cells, we found that IL-10 or/and IL-17 secreting cells prevalently secrete one or the other cytokine depending on the type of stimulation, the time after stimulation and the presence of microbial products. Namely, IL-10 secretion by clonal cells was prevalent at early time points after TCR mediated stimulation, was independent of co-stimulation and was increased in the presence of the microbial fermentation product butyrate. In contrast, IL-17 secretion was higher at later time points after TCR mediated stimulation and in the presence of co-stimulatory signals. Taken together, these results provide insights into the mechanisms that, through modulation of cytokine secretion depending on conditions, allow IL-10 and IL-17 producing CD4 T cells to contribute to maintain tolerance to microbes locally, while retaining the ability to participate in protective immune responses at distant sites.     

Frequency and Extent of Water Limitation to Primary Production in a Mesic Temperate Grassland

The frequency and extent of water limitation to aboveground net primary production (ANPP) in a mesic grassland in NE Kansas (Konza Prairie, USA) was assessed with an 8-year irrigation experiment. Since 1991, transects spanning upland and lowland sites in annually burned, ungrazed tallgrass prairie were provided with supplemental water to satisfy evapotranspirational demands. This protocol minimized water limitations during the growing season, as well as interannual variability in water stress. Irrigation of this mesic grassland increased ANPP in 6 of 8 years by an average of 26% when compared to control transects. Although interannual variation in ANPP was greater in uplands than lowlands at nominal levels of precipitation, reducing interannual variability in water availability via irrigation eliminated topographic differences; the irrigation protocol also reduced interannual variability in ANPP by as much as 40%. The addition of supplemental water enabled us to extend the relationship between annual precipitation and ANPP in grasslands to precipitation levels (average, 1153 mm; maximum, 1346 mm) similar to those experienced by more mesic grasslands that today exist only as remnants several hundred kilometers east of Kansas. This relationship was linear (r ²= 0.81), with maximum ANPP (738 g/m²) similar to values reported for sites in Illinois and Wisconsin. After 8 years of irrigation, production of the C₃ forb component was twice that in control sites. These results indicate that water limitations in grasslands at the western edge of the presettlement extent of tallgrass prairie affect ANPP in most years and that this high frequency of water limitation may lead to greater dominance of the C₄ grasses than is seen in more eastern grassland sites. Received 18 January 2000; accepted 19 July 2000.     

Analysis of Complex Patterns of Human Exposure and Immunity to Schistosomiasis mansoni: The Influence of Age,Sex, Ethnicity and IgE

Background

Numerous factors may influence Schistosoma infection intensity and prevalence within endemic communities, including exposure-related factors such as local environment and behaviour, and factors relating to susceptibility to infection such as immunology and genetics. While animal studies performed in the laboratory can be tightly controlled, human populations are highly heterogeneous, varying according to demographic characteristics, genetic background and exposure to infection. The heterogeneous nature of human water contact behaviour in particular makes it difficult to distinguish between a lack of cercarial exposure and reduced susceptibility to infection as the cause for low levels of infection in the field.

Methods and Principal Findings

In this study we investigate risk factors for Schistosoma mansoni infection in a rural Ugandan fishing community receiving treatment as part of a multi-disciplinary longitudinal reinfection study. More specifically, we examine the influence that age, sex and ethnic background have on susceptibility to reinfection after anti-helminth drug treatment, but use individual estimates of cercarial exposure and multivariable methods in an attempt to remove noise created by environmental and behavioural heterogeneities. We then investigate whether schistosome-specific IgE immune responses could account for any remaining variations in susceptibility to reinfection. Our findings suggest that observed ethnic- and sex-related variations in S. mansoni reinfection were due to variations in cercarial exposure, as opposed to biological differences in susceptibility to infection. Age-related differences in reinfection were not explained by exposure, however, and appeared linked to the balance of IgE and IgG₄ to the tegumental antigen SmTAL1 (formerly Sm22.6), which itself was significantly related to resistance to reinfection.

Conclusions

This study highlights the benefit of taking a multidisciplinary approach in complex field settings; it allows the ecology of a population to be understood and thus more robust conclusions to be made.     

Induction of Immunity and Tolerance to the Dinitrophenyl Determinant <Emphasis Type="Italic">in vitro</Emphasis>

THE immune response in dissociated lymphoid cell cultures offers an opportunity to investigate the interaction of antigen with the surface receptors of immunocompetent cells. Using polymerized flagellin of Salmonella adelaide (POL), evidence was obtained that in vitro processes as different as immunity and tolerance both depend on the direct interaction between antigen and antigen-sensitive cells^1–4. The use of chemically defined determinants in place of natural antigens could simplify the study of the molecular mechanisms underlying immunity and tolerance. Systems used in the past to induce immunity to defined determinants in vitro involved either a particulate antigen⁵ or spleen fragment cultures⁶ and were therefore unsuitable for the detailed study of the interactions occurring on the surface of lymphoid cells. A new system had to be devised. Here I describe the induction of a primary immune response to a hapten–protein conjugate in dissociated spleen cell cultures and the immune tolerance to a chemically defined determinant in vitro.     

Increasing HIV and Decreasing Syphilis Prevalence in a Context of Persistently High Unprotected Anal Intercourse,Six Consecutive Annual Surveys among Men Who Have Sex with Men in Guangzhou,China, 2008 to 2013

Introduction

Previous studies have reported a possibly increasing HIV prevalence among men who have sex with men (MSM) in China. However there have been limited systematic analyses of existing surveillance data to learn the trend of HIV prevalence and factors driving the trend. The aims of this study were to examine the trend of HIV prevalence among MSM in Guangzhou and to explore the role of unprotected anal intercourse (UAI) in the trend.

Methods

Snow-ball sampling was applied in the subject recruitment for the annual serological and behavioral surveys among MSM from 2008 to 2013. Data collected in the behavioral survey include demographic information, HIV related sexual behavior with men and women, access to HIV prevention services, and symptoms of sexually transmitted infections. Chi-square test was used to analyze the trend of HIV prevalence. Multivariate logistic regression was conducted to test the factors associated with HIV infection.

Results

HIV prevalence increased significantly from 5.0% in 2008 to 11.4% in 2013 while syphilis prevalence decreased from 17.4% to 3.3% in the same period. UAI rates were high and stable in every single year, ranging from 54.5% to 62.0%. Those who were having UAI (OR = 1.80, 95% confidence interval (CI): 1.26–2.58), being migrants, having more than 10 partners, and infected with syphilis had higher risk for HIV infection.

Conclusions

HIV epidemic is expanding in Guangzhou. The persistently high UAI may have played a major role in the increasing trend of HIV prevalence. Targeted prevention program should be conducted among MSM who are migrants, low educational level, syphilis infected, or having multiple partners to encourage HIV test and change UAI behavior. The general high UAI calls for tailored intervention program to promote healthy culture and form a safe sex social norm in the MSM community.