Adaptation of mammalian host-pathogen interactions in a changing arctic environment

Many arctic mammals are adapted to live year-round in extreme environments with low winter temperatures and great seasonal variations in key variables (e.g. sunlight, food, temperature, moisture). The interaction between hosts and pathogens in high northern latitudes is not very well understood with respect to intra-annual cycles (seasons). The annual cycles of interacting pathogen and host biology is regulated in part by highly synchronized temperature and photoperiod changes during seasonal transitions (e.g., freezeup and breakup). With a warming climate, only one of these key biological cues will undergo drastic changes, while the other will remain fixed. This uncoupling can theoretically have drastic consequences on host-pathogen interactions. These poorly understood cues together with a changing climate by itself will challenge host populations that are adapted to pathogens under the historic and current climate regime. We will review adaptations of both host and pathogens to the extreme conditions at high latitudes and explore some potential consequences of rapid changes in the Arctic.     

Understanding host utilization by mosquitoes: determinants,challenges and future directions

Mosquito host utilization is a key factor in the transmission of vector-borne pathogens given that it greatly influences host–vector contact rates. Blood-feeding patterns of mosquitoes are not random, as some mosquitoes feed on particular species and/or individuals more than expected by chance. Mosquitoes use a number of cues including visual, olfactory, acoustic, and thermal stimuli emitted by vertebrate hosts to locate and identify their blood meal sources. Thus, differences in the quality/intensity of the released cues may drive host selection by mosquitoes at both inter- and intra-specific levels. Such patterns of host selection by mosquitoes in space and time can be structured by factors related to mosquitoes (e.g. innate host preference, behavioural plasticity), to hosts (e.g. emission of host-seeking cues, host availability) or to both (e.g. pathogen infection). In this study, we review current evidence, from phenomena to mechanisms, of how these factors influence host utilization by mosquitoes. We also review the methodologies commonly used in this research field and identify the major challenges for future studies. To bridge the knowledge gaps, we propose improvements to strengthen traditional approaches and the use of a functional trait-based approach to infer mosquito host utilization in natural communities.     

Loss of Competition in the Outside Host Environment Generates Outbreaks of Environmental Opportunist Pathogens

Environmentally transmitted pathogens face ecological interactions (e.g., competition, predation, parasitism) in the outside-host environment and host immune system during infection. Despite the ubiquitousness of environmental opportunist pathogens, traditional epidemiology focuses on obligatory pathogens incapable of environmental growth. Here we ask how competitive interactions in the outside-host environment affect the dynamics of an opportunist pathogen. We present a model coupling the classical SI and Lotka–Volterra competition models. In this model we compare a linear infectivity response and a sigmoidal infectivity response. An important assumption is that pathogen virulence is traded off with competitive ability in the environment. Removing this trade-off easily results in host extinction. The sigmoidal response is associated with catastrophic appearances of disease outbreaks when outside-host species richness, or overall competition pressure, decreases. This indicates that alleviating outside-host competition with antibacterial substances that also target the competitors can have unexpected outcomes by providing benefits for opportunist pathogens. These findings may help in developing alternative ways of controlling environmental opportunist pathogens.     

Menstrual cycle, pregnancy and oral contraceptive use alter attraction to apparent health in faces

Previous studies demonstrating changes in women's face preferences have emphasized increased attraction to cues to possible indirect benefits (e.g. heritable immunity to infection) that coincides with periods of high fertility (e.g. the late follicular phase of the menstrual cycle). By contrast, here we show that when choosing between composite faces with raised or lowered apparent health, women's preferences for faces that are perceived as healthy are (i) stronger during the luteal phase of the menstrual cycle than during the late follicular, fertile phase, (ii) stronger in pregnant women than in non-pregnant women and (iii) stronger in women using oral contraceptives than in women with natural menstrual cycles. Change in preference for male faces was greater for short- than long-term relationships. These findings indicate raised progesterone level is associated with increased attraction to facial cues associated with possible direct benefits (e.g. low risk of infection) and suggest that women's face preferences are influenced by adaptations that compensate for weakened immune system responses during pregnancy and reduce the risk of infection disrupting foetal development.     

Predicting Aggressive Tendencies by Visual Attention Bias Associated with Hostile Emotions

The goal of the current study is to clarify the relationship between social information processing (e.g., visual attention to cues of hostility, hostility attribution bias, and facial expression emotion labeling) and aggressive tendencies. Thirty adults were recruited in the eye-tracking study that measured various components in social information processing. Baseline aggressive tendencies were measured using the Buss-Perry Aggression Questionnaire (AQ). Visual attention towards hostile objects was measured as the proportion of eye gaze fixation duration on cues of hostility. Hostility attribution bias was measured with the rating results for emotions of characters in the images. The results show that the eye gaze duration on hostile characters was significantly inversely correlated with the AQ score and less eye contact with an angry face. The eye gaze duration on hostile object was not significantly associated with hostility attribution bias, although hostility attribution bias was significantly positively associated with the AQ score. Our findings suggest that eye gaze fixation time towards non-hostile cues may predict aggressive tendencies.     

Schistosome immunomodulators

Schistosomes are long lived, intravascular parasitic platyhelminths that infect >200 million people globally. The molecular mechanisms used by these blood flukes to dampen host immune responses are described in this review. Adult worms express a collection of host-interactive tegumental ectoenzymes that can cleave host signaling molecules such as the “alarmin” ATP (cleaved by SmATPDase1), the platelet activator ADP (SmATPDase1, SmNPP5), and can convert AMP into the anti-inflammatory mediator adenosine (SmAP). SmAP can additionally cleave the lipid immunomodulator sphingosine-1-phosphate and the proinflammatory anionic polymer, polyP. In addition, the worms release a barrage of proteins (e.g., SmCB1, SjHSP70, cyclophilin A) that can impinge on immune cell function. Parasite eggs also release their own immunoregulatory proteins (e.g., IPSE/α1, omega1, SmCKBP) as do invasive cercariae (e.g., Sm16, Sj16). Some schistosome glycans (e.g., LNFPIII, LNnT) and lipids (e.g., Lyso-PS, LPC), produced by several life stages, likewise affect immune cell responses. The parasites not only produce eicosanoids (e.g., PGE2, PGD2—that can be anti-inflammatory) but can also induce host cells to release these metabolites. Finally, the worms release extracellular vesicles (EVs) containing microRNAs, and these too have been shown to skew host cell metabolism. Thus, schistosomes employ an array of biomolecules—protein, lipid, glycan, nucleic acid, and more, to bend host biochemistry to their liking. Many of the listed molecules have been individually shown capable of inducing aspects of the polarized Th2 response seen following infection (with the generation of regulatory T cells (Tregs), regulatory B cells (Bregs) and anti-inflammatory, alternatively activated (M2) macrophages). Precisely how host cells integrate the impact of these myriad parasite products following natural infection is not known. Several of the schistosome immunomodulators described here are in development as novel therapeutics against autoimmune, inflammatory, and other, nonparasitic, diseases.     

Is facial structure an honest cue to real-world dominance and fighting ability in men? A pre-registered direct replication of

Masculine facial morphology (e.g., larger jaw, prominent cheekbones) have been linked to a suite of social outcomes—including greater wealth, career progress, romantic desirability, and even greater political success. A leading explanation for these links is that dominant facial structures represent honest cues of physical dominance and fighting ability. T?ebický et al. (2013) published the first study to demonstrate that masculine facial cues (e.g., large nose, deep-set eyes) similarly predict both dominance judgments and real-world fighting success, but no studies have replicated these popular findings that a large and specific assortment of masculine facial structures are implicated in both fighting ability and dominance perception. Thus, we conducted a pre-registered direct replication and extension of T?ebický et al. (2013). Two separate samples of United States MTurk participants rated 516 UFC fighters' facial photographs on perceived aggressiveness (N = 500) and fighting ability (N = 500). Results showed that perceived aggressiveness was associated with masculine facial morphology (e.g., large nose, deep-set eyes) independent of bodily size. There was also some evidence that perceived fighting ability was associated with masculine facial morphology, which disappeared after controlling for bodily size. There was no support for the relation between facial structure and fighting success, and there were often negative relations between perceived aggressiveness and fighting ability on fighting success (i.e., more successful fighters were perceived as less successful and aggressive). We argue that our evolved psychology differentially processes the distinct avenues to victory that constitute overall fighting success (e.g., knockout versus submission wins).     

Facial Mimicry and Emotion Consistency: Influences of Memory and Context

This study investigates whether mimicry of facial emotions is a stable response or can instead be modulated and influenced by memory of the context in which the emotion was initially observed, and therefore the meaning of the expression. The study manipulated emotion consistency implicitly, where a face expressing smiles or frowns was irrelevant and to be ignored while participants categorised target scenes. Some face identities always expressed emotions consistent with the scene (e.g., smiling with a positive scene), whilst others were always inconsistent (e.g., frowning with a positive scene). During this implicit learning of face identity and emotion consistency there was evidence for encoding of face-scene emotion consistency, with slower RTs, a reduction in trust, and inhibited facial EMG for faces expressing incompatible emotions. However, in a later task where the faces were subsequently viewed expressing emotions with no additional context, there was no evidence for retrieval of prior emotion consistency, as mimicry of emotion was similar for consistent and inconsistent individuals. We conclude that facial mimicry can be influenced by current emotion context, but there is little evidence of learning, as subsequent mimicry of emotionally consistent and inconsistent faces is similar.     

What makes a specialized endophyte special?

Fungal plant symbionts can be highly specialized on a limited range of host genotypes and species. Understanding the genetic basis of this specialization, the mechanisms governing its establishment and the relationship between specialization and speciation is a major challenge for evolutionary biologists (Timms & Read, 1999 ). A deeper knowledge of evolutionary plant–microbe interactions could be exploited to improve agricultural management, by bringing fungal biodiversity and fungal biomass under greater and more durable human control. Previous studies on pathogens have shown that effectors, that is, small secreted proteins that modulate plant physiology to favour host colonization, play a key role in infection of novel hosts (e.g., Inoue et al., 2017 ) or in host specialization (e.g., Liao et al. ( 2016 )). Like pathogens, endophytes also manipulate the physiology of their hosts and colonize novel hosts to which they specialize (Hardoim et al., 2015 ). These biological characteristics of endophytes raise the question of similarities in the protein arsenal contributing to the specialization of pathogens and endophytes. In this issue of Molecular Ecology, Schirrmann et al. ( 2018 ) used a combination of divergence genome scans and tests for positive selection to investigate the genetic basis of specialization of two subspecies of the symbiont Epichloë typhina occurring on two different grass hosts. Their analyses suggest a key role of effectors as determinants of host specialization. This study paves the way towards the comparative analysis of the genomics of speciation among plant symbionts.     

A role for altered phagosome maturation in the long-term persistence of Helicobacter pylori infection

The vigorous host immune response that is mounted against Helicobacter pylori is unable to eliminate this pathogenic bacterium from its niche in the human gastric mucosa. This results in chronic inflammation, which can develop into gastric or duodenal ulcers in 10% of infected individuals and gastric cancer in 1% of infections. The determinants for these more severe pathologies include host (e.g., high IL-1β expression polymorphisms), bacterial [e.g., cytotoxicity-associated gene (cag) pathogenicity island], and environmental (e.g., dietary nitrites) factors. However, it is the failure of host immune effector cells to eliminate H. pylori that underlies its persistence and the subsequent H. pylori-associated disease. Here we discuss the mechanisms used by H. pylori to survive the host immune response and, in particular, the role played by altered phagosome maturation.     

No evidence of sickness behavior in immune‐challenged field crickets

Sickness behavior is a taxonomically widespread coordinated set of behavioral changes that increases shelter‐seeking while reducing levels of general activity, as well as food (anorexia) and water (adipsia) consumption, when fighting infection by pathogens and disease. The leading hypothesis explaining such sickness‐related shifts in behavior is the energy conservation hypothesis. This hypothesis argues that sick (i.e., immune‐challenged) animals reduce energetic expenditure in order have more energy to fuel an immune response, which in some vertebrates, also includes producing an energetically expensive physiological fever. We experimentally tested the hypothesis that an immune challenge with lipopolysaccharide (LPS) will cause Gryllus firmus field crickets to reduce their activity, increase shelter use and avoid foods that interfere with an immune response (i.e., fat) while preferring a diet that fuels an immune response (i.e., protein). We found little evidence of sickness behavior in Gryllus firmus as immune‐challenged individuals did not reduce their activity or increase their shelter‐seeking. Neither did we observe changes in feeding or drinking behavior nor a preference for protein or avoidance of lipids. Males tended to use shelters less than females but no other behaviors differed between the sexes. The lack of sickness behavior in our study might reflect the fact that invertebrates do not possess energetically expensive physiological fever as part of their immune response. Therefore, there is little reason to conserve energy via reduced activity or increased shelter use when immune‐challenged.     

An integrated model of the recognition of Candida albicans by the innate immune system

The innate immune response was once considered to be a limited set of responses that aimed to contain an infection by primitive 'ingest and kill' mechanisms, giving the host time to mount a specific humoral and cellular immune response. In the mid-1990s, however, the discovery of Toll-like receptors heralded a revolution in our understanding of how microorganisms are recognized by the innate immune system, and how this system is activated. Several major classes of pathogen-recognition receptors have now been described, each with specific abilities to recognize conserved bacterial structures. The challenge ahead is to understand the level of complexity that underlies the response that is triggered by pathogen recognition. In this Review, we use the fungal pathogen Candida albicans as a model for the complex interaction that exists between the host pattern-recognition systems and invading microbial pathogens.     

Beneficial microbes going underground of root immunity

Plant roots interact with an enormous diversity of commensal, mutualistic, and pathogenic microbes, which poses a big challenge to roots to distinguish beneficial microbes from harmful ones. Plants can effectively ward off pathogens following immune recognition of conserved microbe‐associated molecular patterns (MAMPs). However, such immune elicitors are essentially not different from those of neutral and beneficial microbes that are abundantly present in the root microbiome. Recent studies indicate that the plant immune system plays an active role in influencing rhizosphere microbiome composition. Moreover, it has become increasingly clear that root‐invading beneficial microbes, including rhizobia and arbuscular mycorrhiza, evade or suppress host immunity to establish a mutualistic relationship with their host. Evidence is accumulating that many free‐living rhizosphere microbiota members can suppress root immune responses, highlighting root immune suppression as an important function of the root microbiome. Thus, the gate keeping functions of the plant immune system are not restricted to warding off root‐invading pathogens but also extend to rhizosphere microbiota, likely to promote colonization by beneficial microbes and prevent growth‐defense tradeoffs triggered by the MAMP‐rich rhizosphere environment.     

Acute or chronic? Within-host models with immune dynamics, infection outcome, and parasite evolution

There is ample theoretical and experimental evidence that virulence evolution depends on the immune response of the host. In this article, we review a number of recent studies that attempt to explicitly incorporate the dynamics of the immune system (instead of merely representing it by a single black box parameter) in models for the evolution of parasite virulence. A striking observation is that the type of infection (acute or chronic) is invariably considered to be a constraint that model assumptions have to satisfy rather than as a potential outcome of the interaction of the parasite with its host's immune system. We argue that avoiding making assumptions about the type of infection will lead to a better understanding of infectious diseases, even though a number of fundamental and technical problems remain. Dynamical modeling of the immune system opens a wide range of perspectives: for understanding how the immune system eradicates a parasite (which it does for most pathogens but not for all, HIV being a notorious example of a virus that is not completely eliminated), for studying multiple infections through concomitant immunity, for understanding the emergence and evolution of the immune system in animals, and for evolutionary epidemiology in general (e.g., predicting evolutionary consequences of new therapies and public health policies). We conclude by discussing new approaches based on embedded (or nested) models and identify future perspectives for the modeling of infectious diseases.     

Emotional Modulation of Attention: Fear Increases but Disgust Reduces the Attentional Blink

Background

It is well known that facial expressions represent important social cues. In humans expressing facial emotion, fear may be configured to maximize sensory exposure (e.g., increases visual input) whereas disgust can reduce sensory exposure (e.g., decreases visual input). To investigate whether such effects also extend to the attentional system, we used the “attentional blink” (AB) paradigm. Many studies have documented that the second target (T2) of a pair is typically missed when presented within a time window of about 200–500 ms from the first to-be-detected target (T1; i.e., the AB effect). It has recently been proposed that the AB effect depends on the efficiency of a gating system which facilitates the entrance of relevant input into working memory, while inhibiting irrelevant input. Following the inhibitory response on post T1 distractors, prolonged inhibition of the subsequent T2 is observed. In the present study, we hypothesized that processing facial expressions of emotion would influence this attentional gating. Fearful faces would increase but disgust faces would decrease inhibition of the second target.

Methodology/Principal Findings

We showed that processing fearful versus disgust faces has different effects on these attentional processes. We found that processing fear faces impaired the detection of T2 to a greater extent than did the processing disgust faces. This finding implies emotion-specific modulation of attention.

Conclusions/Significance

Based on the recent literature on attention, our finding suggests that processing fear-related stimuli exerts greater inhibitory responses on distractors relative to processing disgust-related stimuli. This finding is of particular interest for researchers examining the influence of emotional processing on attention and memory in both clinical and normal populations. For example, future research could extend upon the current study to examine whether inhibitory processes invoked by fear-related stimuli may be the mechanism underlying the enhanced learning of fear-related stimuli.     

Unfakeable facial configurations affect strategic choices in trust games with or without information about past behavior

Background

Many human interactions are built on trust, so widespread confidence in first impressions generally favors individuals with trustworthy-looking appearances. However, few studies have explicitly examined: 1) the contribution of unfakeable facial features to trust-based decisions, and 2) how these cues are integrated with information about past behavior.

Methodology/Principal Findings

Using highly controlled stimuli and an improved experimental procedure, we show that unfakeable facial features associated with the appearance of trustworthiness attract higher investments in trust games. The facial trustworthiness premium is large for decisions based solely on faces, with trustworthy identities attracting 42% more money (Study 1), and remains significant though reduced to 6% when reputational information is also available (Study 2). The face trustworthiness premium persists with real (rather than virtual) currency and when higher payoffs are at stake (Study 3).

Conclusions/Significance

Our results demonstrate that cooperation may be affected not only by controllable appearance cues (e.g., clothing, facial expressions) as shown previously, but also by features that are impossible to mimic (e.g., individual facial structure). This unfakeable face trustworthiness effect is not limited to the rare situations where people lack any information about their partners, but survives in richer environments where relevant details about partner past behavior are available.     

Key thermally dimorphic fungal pathogens: shaping host immunity

Exposure to fungal pathogens from the environment is inevitable and with the number of at-risk populations increasing, the prevalence of invasive fungal infection is on the rise. An interesting group of fungal organisms known as thermally dimorphic fungi predominantly infects immunocompromised individuals. These potential pathogens are intriguing in that they survive in the environment in one form, mycelial phase, but when entering the host, they are triggered by the change in temperature to switch to a new pathogenic form. Considering the growing prevalence of infection and the need for improved diagnostic and treatment approaches, studies identifying key components of fungal recognition and the innate immune response to these pathogens will significantly contribute to our understanding of disease progression. This review focuses on key endemic dimorphic fungal pathogens that significantly contribute to disease, including Histoplasma, Coccidioides and Talaromyces species. We briefly describe their prevalence, route of infection and clinical presentation. Importantly, we have reviewed the major fungal cell wall components of these dimorphic fungi, the host pattern recognition receptors responsible for recognition and important innate immune responses supporting adaptive immunity and fungal clearance or the failure thereof.     

Loneliness and Hypervigilance to Social Cues in Females: An Eye-Tracking Study

The goal of the present study was to examine whether lonely individuals differ from nonlonely individuals in their overt visual attention to social cues. Previous studies showed that loneliness was related to biased post-attentive processing of social cues (e.g., negative interpretation bias), but research on whether lonely and nonlonely individuals also show differences in an earlier information processing stage (gazing behavior) is very limited. A sample of 25 lonely and 25 nonlonely students took part in an eye-tracking study consisting of four tasks. We measured gazing (duration, number of fixations and first fixation) at the eyes, nose and mouth region of faces expressing emotions (Task 1), at emotion quadrants (anger, fear, happiness and neutral expression) (Task 2), at quadrants with positive and negative social and nonsocial images (Task 3), and at the facial area of actors in video clips with positive and negative content (Task 4). In general, participants tended to gaze most often and longest at areas that conveyed most social information, such as the eye region of the face (T1), and social images (T3). Participants gazed most often and longest at happy faces (T2) in still images, and more often and longer at the facial area in negative than in positive video clips (T4). No differences occurred between lonely and nonlonely participants in their gazing times and frequencies, nor at first fixations at social cues in the four different tasks. Based on this study, we found no evidence that overt visual attention to social cues differs between lonely and nonlonely individuals. This implies that biases in social information processing of lonely individuals may be limited to other phases of social information processing. Alternatively, biased overt attention to social cues may only occur under specific conditions, for specific stimuli or for specific lonely individuals.     

Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses

Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options.     

Vying for the control of inflammasomes: The cytosolic frontier of enteric bacterial pathogen–host interactions

Enteric pathogen–host interactions occur at multiple interfaces, including the intestinal epithelium and deeper organs of the immune system. Microbial ligands and activities are detected by host sensors that elicit a range of immune responses. Membrane‐bound toll‐like receptors and cytosolic inflammasome pathways are key signal transducers that trigger the production of pro‐inflammatory molecules, such as cytokines and chemokines, and regulate cell death in response to infection. In recent years, the inflammasomes have emerged as a key frontier in the tussle between bacterial pathogens and the host. Inflammasomes are complexes that activate caspase‐1 and are regulated by related caspases, such as caspase‐11, ‐4, ‐5 and ‐8. Importantly, enteric bacterial pathogens can actively engage or evade inflammasome signalling systems. Extracellular, vacuolar and cytosolic bacteria have developed divergent strategies to subvert inflammasomes. While some pathogens take advantage of inflammasome activation (e.g. Listeria monocytogenes, Helicobacter pylori), others (e.g. E. coli, Salmonella, Shigella, Yersinia sp.) deploy a range of virulence factors, mainly type 3 secretion system effectors, that subvert or inhibit inflammasomes. In this review we focus on inflammasome pathways and their immune functions, and discuss how enteric bacterial pathogens interact with them. These studies have not only shed light on inflammasome‐mediated immunity, but also the exciting area of mammalian cytosolic immune surveillance.