Hormonal correlates of pathogen disgust: testing the compensatory prophylaxis hypothesis

Raised progesterone during the menstrual cycle is associated with suppressed physiological immune responses, reducing the probability that the immune system will compromise the blastocyst's development. The Compensatory Prophylaxis Hypothesis proposes that this progesterone-linked immunosuppression triggers increased disgust responses to pathogen cues, compensating for the reduction in physiological immune responses by minimizing contact with pathogens. Although a popular and influential hypothesis, there is no direct, within-woman evidence for correlated changes in progesterone and pathogen disgust. To address this issue, we used a longitudinal design to test for correlated changes in salivary progesterone and pathogen disgust (measured using the pathogen disgust subscale of the Three Domain Disgust Scale) in a large sample of women (N = 375). Our analyses showed no evidence that pathogen disgust tracked changes in progesterone, estradiol, testosterone, or cortisol. Thus, our results provide no support for the Compensatory Prophylaxis Hypothesis of variation in pathogen disgust.     

Pathogen disgust,but not moral disgust,changes across the menstrual cycle

The Compensatory Prophylaxis Hypothesis (CPH) proposes that during periods of increased susceptibility to infections, e.g., during the luteal phase of the menstrual cycle when progesterone suppresses immune function, women should feel more disgust toward pathogen cues and behave prophylactically. We investigate differences in disgust sensitivity and contamination sensitivity during different phases of the menstrual cycle in regularly cycling, healthy 93 rural and urban Polish women using the within-subject design. Disgust sensitivity was measured during two different phases of a menstrual cycle: 1) the follicular phase (the 5th or 6th day of the cycle) and 2) the luteal phase (on the 5th day after a positive ovulatory test or on 20th day of a cycle if the result of the ovulatory test was not positive). In the luteal phase, women scored higher on the Pathogen Disgust of the Three-Domain Disgust Scale, the Contamination Obsessions and Washing Compulsions Subscale of Padua Inventory, and on ratings of photographs showing sources of potential infections than in the follicular phase. Moral Disgust of the Three-Domain Disgust Scale did not differ between cycle phases. Hence, results suggest that women feel more disgusted toward cues to pathogens during the luteal phase, when susceptibility to infection is greater. We suggest that it is necessary to incorporate ovulatory testing as well as to conduct repeated measurements of disgust sensitivity in future tests of the CPH. Moreover, we believe that understanding how the feeling of pathogen disgust varies across the menstrual cycle and in relation to progesterone levels could be useful in designing effective infectious diseases prevention strategies for women.     

Disgust sensitivity is negatively associated with immune system activity in early pregnancy: Direct support for the Compensatory Prophylaxis Hypothesis

According to the Compensatory Prophylaxis Hypothesis (CPH), disgust may be considered a part of the behavioral immune system, adjusting as a function of immunocompetence. Early pregnancy involves modulation of a complex network of various immune-related factors, but only a few studies so far have focused on disgust sensitivity in pregnant women in the context of the CPH. This study aimed to examine associations between disgust sensitivity and immune activity indices, cytokine levels, and white blood cell (WBC) count in pregnant women. The sample included 78 women in the 1st trimester of pregnancy. Higher disgust sensitivity (Disgust Scale-Revised; DS-R) was significantly associated with decreased levels of IL-1β, IL-2 IL-4, IL-7, IL-17, Eotaxin, MCP-1 (MCAF), and RANTES in blood serum. This model explained 17.5% of the total DS-R score variability. Using the DS-R subscales, the Contamination disgust was significantly associated with levels of FGF basic, IFN-γ, IL-1β, IL-2, IL-4, IL-7, IL-17A, G-CSF, MCP-1 (MCAF), MIP-1α, PDGF-BB, and RANTES, and the Core disgust was significantly associated with levels of IL-1β, IL-2, IL-4, IL-7, IL-17A, Eotaxin, G-CSF, IP-10, MCP-1 (MCAF), PDGF-BB, and TNF-α. Disgust sensitivity was not associated with WBC count. Disgust may reflect and compensate for insufficient immune adaptation in early pregnancy, suggesting the potential clinical significance of this common prenatal symptom.     

Domain-specific variation in disgust sensitivity across the menstrual cycle

Disgust operates in many domains of behavior. On the presumption that facets of this emotion evince adaptive design, we conducted a cross-sectional study of 307 women, investigating changes in disgust sensitivity across the menstrual cycle. Two hypotheses were tested, namely (i) sexual disgust is an adaptation that serves to reduce participation in biologically suboptimal sexual behaviors, and (ii) many facets of disgust sensitivity compensate for cyclic changes in immunological robusticity via patterned alterations in behavioral prophylaxis against pathogens. Hypothesis (i) was supported, as disgust sensitivity in the sexual domain, and only in the sexual domain, was positively correlated with presumed conception risk as assessed on the basis of self-reported position in the menstrual cycle. Hypothesis (ii) was not supported, as no facet of disgust sensitivity changed as a function of the presumed level of immunosuppression assessed on the basis of self-reported position in the menstrual cycle. Results are discussed in light of published ethnographic evidence indicating that, in disparate cultures, disgust is elicited by aberrant sexual behaviors, and sex is equated with eating. Together with published findings on an animal model of sexual conditioning, this corpus suggests that sexual disgust may be a panmammalian adaptation.     

Disgust sensitivity predicts sociosexuality across cultures

Restricted sociosexuality has been linked to sexual disgust, suggesting that decreasing sexual behavior may be a pathogen avoidance technique. Using the behavioral immune system framework, which posits that humans experience disgust after exposure to pathogen cues, we replicate and expand on previous studies by analyzing the influence of three domains of disgust (sexual, moral, pathogen) on psychological (desire and attitude) and behavioral domains of sociosexuality (SOI) in four diverse samples: American university students (n = 155), Salvadoran community members (n = 98), a global online sample (n = 359), and a four-country online sample (US, India, Italy, and Brazil; n = 822) collected during the SARS-CoV-2 pandemic. In contrast with previous studies, we account for shared variance in sexual, pathogen, and moral disgust by entering all three in a multiple regression to predict composite SOI. In both large samples, sexual disgust and pathogen disgust had opposing effects on composite SOI; that is, higher sexual disgust and lower pathogen disgust were associated with more restricted composite SOI. Additionally, we constructed a multi-group structural equation model (SEM) to determine the impact of each domain of disgust on each domain of SOI across all our samples simultaneously, while controlling for age and sex. Within this model we also assessed how the psychological domains of SOI – attitude and desire – mediate the relationship between disgust and sociosexual behavior. Pathogen disgust positively predicted SOI attitude and desire, but not behavior, consistently across all groups. SOI behavior was only predicted by pathogen disgust when mediated by SOI attitude, again across all groups, suggesting that behavior seems to be driven largely by the psychological facets of SOI. We discuss these findings in light of the behavioral immune system and the bet-hedging hypothesis, which make opposing predictions on the relationship between infection risk and sexual behavior.     

Examining the effect of hunger on responses to pathogen cues and novel foods

Although multiple leading papers in the behavioral immune system literature have proposed that food deprivation affects responses to pathogen cues, evidence supporting this proposition is scarce. Here, we report results from what we believe to be the most comprehensive test of the effects of hunger on responses to pathogen cues to date. Participants (N = 40) recruited from a Dutch university attended two experimental sessions, each following a 15-hour fast. One of the two sessions was conducted immediately after eating a standardized meal, and the other was conducted before eating that same standardized meal. In each session, participants rated 40 different images (i.e., images depicting food-related pathogen cues, food-unrelated pathogen cues, violence, positive stimuli, and neutral stimuli) on valence and arousal while their heart rate and skin conductance responses were recorded. They also indicated their willingness to eat 16 novel foods. Results did not reveal an effect of nutritional state on explicit ratings of and physiological reactions to food-related or food-unrelated pathogen cues. However, participants reported a greater willingness to eat novel foods when hungry than when sated. These results raise doubt regarding proposals that short-term changes in nutritional state influence responses to pathogen cues, but they suggest that these same changes increase willingness to eat novel foods.     

Investigating the relationship between olfactory acuity,disgust, and mating strategies

Although humans' sense of smell is relatively diminished compared to other species, olfaction is still a central sensory modality through which people evaluate both potential threats and prospective romantic partners. Despite olfaction's role in interpersonal relationships and disease avoidant responses, however, it remains unknown whether variation in olfactory acuity is associated with disease- and mating-relevant psychological constructs and behaviors. In the current exploratory study, we examined the relationships between olfactory acuity, disgust sensitivity, and mating strategies in a sample of undergraduate students (N = 162) at a university in the Southern United States using an extended assessment of olfactory acuity (measuring olfactory threshold, discrimination, and identification). Results revealed that people with greater discrimination acuity were higher in dispositional sexual disgust, but not pathogen or moral disgust. People with greater discrimination acuity were also less inclined towards short-term mating. Further, sexual disgust mediated the relationship between discrimination acuity and short-term mating orientation. These results provide further evidence for the importance of olfaction and olfaction-related disgust in close relationships.     

Exposure to Bacterial Signals Does Not Alter Pea Aphids’ Survival upon a Second Challenge or Investment in Production of Winged Offspring

Pea aphids have an obligate nutritional symbiosis with the bacteria Buchnera aphidicola and frequently also harbor one or more facultative symbionts. Aphids are also susceptible to bacterial pathogen infections, and it has been suggested that aphids have a limited immune response towards such pathogen infections compared to other, more well-studied insects. However, aphids do possess at least some of the genes known to be involved in bacterial immune responses in other insects, and immune-competent hemocytes. One possibility is that immune priming with microbial elicitors could stimulate immune protection against subsequent bacterial infections, as has been observed in several other insect systems. To address this hypothesis we challenged aphids with bacterial immune elicitors twenty-four hours prior to live bacterial pathogen infections and then compared their survival rates to aphids that were not pre-exposed to bacterial signals. Using two aphid genotypes, we found no evidence for immune protection conferred by immune priming during infections with either Serratia marcescens or with Escherichia coli. Immune priming was not altered by the presence of facultative, beneficial symbionts in the aphids. In the absence of inducible immune protection, aphids may allocate energy towards other defense traits, including production of offspring with wings that could escape deteriorating conditions. To test this, we monitored the ratio of winged to unwinged offspring produced by adult mothers of a single clone that had been exposed to bacterial immune elicitors, to live E. coli infections or to no challenge. We found no correlation between immune challenge and winged offspring production, suggesting that this mechanism of defense, which functions upon exposure to fungal pathogens, is not central to aphid responses to bacterial infections.     

Condition-dependent alteration of cellular immunity by secondary symbionts in the pea aphid,Acyrthosiphon pisum

Endosymbionts can fundamentally alter host physiology. Whether such changes are beneficial or detrimental to one or both partners may depend on the dynamics of the symbiotic relationship. Here we investigate the relationship between facultative symbionts and host immune responses. The pea aphid, Acyrthosiphon pisum, maintains an obligate primary symbiont, but may also harbour one or more facultative, secondary symbionts. Given their more transient nature and relatively recent adoption of a symbiotic lifestyle compared to primary symbionts, secondary symbionts may present a challenge for the host immune system. We assessed the response of several key components of the cellular immune system (phenoloxidase activity, encapsulation, immune cell counts) in the presence of alternative secondary symbionts, investigating the role of host and secondary symbiont genotype in specific responses. There was no effect of secondary symbiont presence on the phenoloxidase response, but we found variation in the encapsulation response and in immune cell counts based largely on the secondary symbiont. Host genotype was less influential in determining immunity outcomes. Our results highlight the importance of secondary symbionts in shaping host immunity. Understanding the complex physiological responses that can be propagated by host-symbiont associations has important consequences for host ecology, including symbiont and pathogen transmission dynamics.     

Disgust versus Lust: Exploring the Interactions of Disgust and Fear with Sexual Arousal in Women

Sexual arousal is a motivational state that moves humans toward situations that inherently pose a risk of disease transmission. Disgust is an emotion that adaptively moves humans away from such situations. Incongruent is the fact that sexual activity is elementary to human fitness yet involves strong disgust elicitors. Using an experimental paradigm, we investigated how these two states interact. Women (final N=76) were assigned to one of four conditions: rate disgust stimuli then watch a pornographic clip; watch a pornographic clip then rate disgust stimuli; rate fear stimuli then watch a pornographic clip; or watch a pornographic clip then rate fear stimuli. Women’s genital sexual arousal was measured with vaginal photoplethysmography and their disgust and fear reactions were measured via self-report. We did not find that baseline disgust propensity predicted sexual arousal in women who were exposed to neutral stimuli before erotic content. In the Erotic-before-Disgust condition we did not find that sexual arousal straightforwardly predicted decreased image disgust ratings. However, we did find some evidence that sexual arousal increased self-reported disgust in women with high trait disgust and sexual arousal decreased self-reported disgust in women with low trait disgust. Women who were exposed to disgusting images before erotic content showed significantly less sexual arousal than women in the control condition or women exposed to fear-inducing images before erotic content. In the Disgust-before-Erotic condition the degree of self-reported disgust was negatively correlated with genital sexual arousal. Hence, in the conflict between the ultimate goals of reproduction and disease avoidance, cues of the presence of pathogens significantly reduce the motivation to engage in mating behaviors that, by their nature, entail a risk of pathogen transmission.     

Climate change,nutrition and immunity: Effects of elevated CO2 and temperature on the immune function of an insect herbivore

Balanced nutrition is fundamental to health and immunity. For herbivorous insects, nutrient-compositional shifts in host plants due to elevated atmospheric CO₂ concentrations and temperature may compromise this balance. Therefore, understanding their immune responses to such shifts is vital if we are to predict the outcomes of climate change for plant–herbivore–parasitoid and pathogen interactions. We tested the immune response of Paropsis atomaria Olivier (Coleoptera: Chrysomelidae) feeding on Eucalyptus tereticornis Sm. seedlings exposed to elevated CO₂ (640 μmol mol⁻¹; C_E) and temperature (ambient plus 4 °C; T_E). Larvae were immune-challenged with a nylon monofilament in order to simulate parasitoid or pathogen attack without other effects of actual parasitism or pathology. The cellular (in vivo melanisation) and humoral (in vitro phenoloxidase PO activity) immune responses were assessed, and linked to changes in leaf chemistry. C_E reduced foliar nitrogen (N) concentrations and increased C:N ratios and concentrations of total phenolics. The humoral response was reduced at C_E. PO activity and haemolymph protein concentrations decreased at C_E, while haemolymph protein concentrations were positively correlated with foliar N concentrations. However, the cellular response increased at C_E and this was not correlated with any foliar traits. Immune parameters were not impacted by T_E. Our study revealed that opposite cellular and humoral immune responses occurred as a result of plant-mediated effects at C_E. In contrast, elevated temperatures within the tested range had minimal impact on immune responses. These complex interactions may alter the outcomes of parasitoid and pathogen attack in future climates.     

Natural Transmission of Plasmodium berghei Exacerbates Chronic Tuberculosis in an Experimental Co-Infection Model

Human populations are rarely exposed to one pathogen alone. Particularly in high incidence regions such as sub-Saharan Africa, concurrent infections with more than one pathogen represent a widely underappreciated public health problem. Two of the world’s most notorious killers, malaria and tuberculosis, are co-endemic in impoverished populations in the tropics. However, interactions between both infections in a co-infected individual have not been studied in detail. Both pathogens have a major impact on the lung as the prime target organ for aerogenic Mycobacterium tuberculosis and the site for one of the main complications in severe malaria, malaria-associated acute respiratory distress syndrome (MA-ARDS). In order to study the ramifications caused by both infections within the same host we established an experimental mouse model of co-infection between Mycobacterium tuberculosis and Plasmodium berghei NK65, a recently described model for MA-ARDS. Our study provides evidence that malaria-induced immune responses impair host resistance to Mycobacterium tuberculosis. Using the natural routes of infection, we observed that co-infection exacerbated chronic tuberculosis while rendering mice less refractory to Plasmodium. Co-infected animals presented with enhanced inflammatory immune responses as reflected by exacerbated leukocyte infiltrates, tissue pathology and hypercytokinemia accompanied by altered T-cell responses. Our results - demonstrating striking changes in the immune regulation by co-infection with Plasmodium and Mycobacterium - are highly relevant for the medical management of both infections in humans.     

Behavioral and Immune Responses to Infection Require G��q- RhoA Signaling in C. elegans

Following pathogen infection the hosts'' nervous and immune systems react with coordinated responses to the danger. A key question is how the neuronal and immune responses to pathogens are coordinated, are there common signaling pathways used by both responses? Using C. elegans we show that infection by pathogenic strains of M. nematophilum, but not exposure to avirulent strains, triggers behavioral and immune responses both of which require a conserved Gαq-RhoGEF Trio-Rho signaling pathway. Upon infection signaling by the Gαq pathway within cholinergic motorneurons is necessary and sufficient to increase release of the neurotransmitter acetylcholine and increase locomotion rates and these behavioral changes result in C. elegans leaving lawns of M. nematophilum. In the immune response to infection signaling by the Gαq pathway within rectal epithelial cells is necessary and sufficient to cause changes in cell morphology resulting in tail swelling that limits the infection. These Gαq mediated behavioral and immune responses to infection are separate, act in a cell autonomous fashion and activation of this pathway in the appropriate cells can trigger these responses in the absence of infection. Within the rectal epithelium the Gαq signaling pathway cooperates with a Ras signaling pathway to activate a Raf-ERK-MAPK pathway to trigger the cell morphology changes, whereas in motorneurons Gαq signaling triggers behavioral responses independent of Ras signaling. Thus, a conserved Gαq pathway cooperates with cell specific factors in the nervous and immune systems to produce appropriate responses to pathogen. Thus, our data suggests that ligands for Gq coupled receptors are likely to be part of the signals generated in response to M. nematophilum infection.     

Testing Cort-Fitness and Cort-Adaptation hypotheses in a habitat suitability gradient for roe deer

According to the Cort-Fitness Hypothesis, higher stress levels (glucocorticoids) in vertebrates are correlated to lower fitness. However, recent studies have failed to validate this hypothesis. A proposed wider framework suggests that reproduction can be perceived as an overload adds up to other environmental challenges that individuals must adjust to. In this case, elevated glucocorticoids could help individuals to allocate resources to reproduction without comprising other functions, leading to the expectation of a positive cort-fitness relationship. This has been proposed as the Cort-Adaptation Hypothesis. Stress levels result from a complex interaction between the environment and the neuroendocrine system of animals. Accounting for physiological functions involved in how animals cope with their environment would help to clarify the relationship between glucocorticoids and animal performance. We used roe deer (Capreolus capreolus) inhabiting diverse habitats in the Iberian Peninsula to: i) test the Cort-Fitness and Cort-Adaptation hypotheses by indexing fitness using a comprehensive physiological approach which takes into account fundamental physiological functions and their trade-offs; and ii) evaluate the link between primary productivity and individuals' condition in a seasonal environment. We evaluated spatial and temporal variation in stress levels, reproductive hormone levels, nutritional status and immune function from fecal samples collected in 2010. Lower stress levels were related to better condition in non-reproductive seasons but not to higher primary productivity. In contrast, stress levels were always positively related to reproductive condition, which was better in most productive habitats. Summer and winter were the less productive seasons and the more challenging for the species in the habitat gradient studied. In winter, reproductive condition traded off against immune function being biased toward immune function in less productive habitats. In summer reduced primary productivity limited roe deer nutritional and immunological condition but not reproductive condition. Overall our results match both the Cort-Fitness and Cort-Adaptation Hypotheses.     

Are physiological and behavioral immune responses negatively correlated? Evidence from hormone-linked differences in men's face preferences

Behaviors that minimize exposure to sources of pathogens can carry opportunity costs. Consequently, how individuals resolve the tradeoff between the benefits and costs of behavioral immune responses should be sensitive to the extent to which they are vulnerable to infectious diseases. However, although it is a strong prediction of this functional flexibility principle, there is little compelling evidence that individuals with stronger physiological immune responses show weaker behavioral immune responses. Here we show that men with the combination of high testosterone and low cortisol levels, a hormonal profile recently found to be associated with particularly strong physiological immune responses, show weaker preferences for color cues associated with carotenoid pigmentation. Since carotenoid cues are thought to index vulnerability to infectious illnesses, our results are consistent with the functional flexibility principle's prediction that individuals with stronger physiological immune responses show weaker behavioral immune responses.     

Women's preferences for masculinity in male faces are predicted by pathogen disgust,but not by moral or sexual disgust

Because women's preferences for male masculinity reflect tradeoffs between the benefits of greater genetic health and the costs of lower paternal investment, variables that affect the importance of these costs and benefits also affect masculinity preferences. Concern about disease and pathogens may be one such variable. Here we show that disgust sensitivity in the pathogen domain is positively correlated with facial masculinity preferences, but disgust sensitivity in the moral and sexual domains is not. Our findings present novel evidence that systematic variation in women's preferences for masculine men reflects factors that influence how women resolve the tradeoff between the benefits and costs associated with choosing a masculine partner.     

Re-evaluating the relationship between pathogen avoidance and preferences for facial symmetry and sexual dimorphism: A registered report

Over the past decade, a small literature has tested how trait-level pathogen-avoidance motives (e.g., disgust sensitivity) and exposure to pathogen cues relate to preferences for facial symmetry and sexual dimorphism. Results have largely been interpreted as suggesting that the behavioral immune system influences preferences for these features in potential mates. However, findings are limited by small sample sizes among studies reporting supportive evidence, the use of small stimulus sets to assess preferences for symmetry and dimorphism, and design features that render implications for theory ambiguous (namely, largely only investigating women's preferences for male faces). Using a sample of 954 White young adult UK participants and a pool of 100 White young adult stimuli, the current registered report applied a standard two-alternative forced-choice approach to evaluate both men's and women's preferences for both facial symmetry and dimorphism in both same- and opposite-sex targets. Participants were randomly assigned to either a pathogen prime or a control prime, and they completed instruments assessing individual differences in pathogen avoidance (disgust sensitivity and contamination sensitivity). Results revealed overall preferences for both facial symmetry and dimorphism. However, they did not reveal a relation between these preferences and disgust sensitivity or contamination sensitivity, nor did they reveal differences in these preferences across control and pathogen prime conditions. Null results of pathogen-avoidance variables were consistent across participant sex, target sex, and interactions between participant sex and target sex. Overall, findings cast doubt on the hypothesis that pathogen-avoidance motives influence preferences for facial symmetry or dimorphism.     

Increased inflammatory response in aged mice is associated with age-related zinc deficiency and zinc transporter dysregulation

Aging is a complex process associated with physiological changes in numerous organ systems. In particular, aging of the immune system is characterized by progressive dysregulation of immune responses, resulting in increased susceptibility to infectious diseases, impaired vaccination efficacy and systemic low-grade chronic inflammation. Increasing evidence suggest that intracellular zinc homeostasis, regulated by zinc transporter expression, is critically involved in the signaling and activation of immune cells. We hypothesize that epigenetic alterations and nutritional deficits associated with aging may lead to zinc transporter dysregulation, resulting in decreases in cellular zinc levels and enhanced inflammation with age. The goal of this study was to examine the contribution of age-related zinc deficiency and zinc transporter dysregulation on the inflammatory response in immune cells. The effects of zinc deficiency and age on the induction of inflammatory responses were determined using an in vitro cell culture system and an aged mouse model. We showed that zinc deficiency, particularly the reduction in intracellular zinc in immune cells, was associated with increased inflammation with age. Furthermore, reduced Zip 6 expression enhanced proinflammatory response, and age-specific Zip 6 dysregulation correlated with an increase in Zip 6 promoter methylation. Furthermore, restoring zinc status via dietary supplementation reduced aged-associated inflammation. Our data suggested that age-related epigenetic dysregulation in zinc transporter expression may influence cellular zinc levels and contribute to increased susceptibility to inflammation with age.     

An S-locus receptor-like kinase plays a role as a negative regulator in plant defense responses

Plant cells often use cell surface receptors to sense environmental changes and then transduce external signals via activated signaling pathways to trigger adaptive responses. In Arabidopsis, the receptor-like protein kinase (RLK) gene family contains more than 600 members, and some of these are induced by pathogen infection, suggesting a possible role in plant defense responses. We previously characterized an S-locus RLK (CBRLK1) at the biochemical level. In this study, we examined the physiological function of CBRLK1 in defense responses. CBRLK1 mutant and CBRLK1-overexpressing transgenic plants showed enhanced and reduced resistance against a virulent bacterial pathogen, respectively. The altered pathogen resistances of the mutant and overexpressing transgenic plants were associated with increased and reduced induction of the pathogenesis-related gene PR1, respectively. These results suggest that CBRLK1 plays a negative role in the disease resistance signaling pathway in Arabidopsis.