Humans exhibit considerable variation in their susceptibility to both infectious and chronic diseases (i.e. immunodeficiency viruses, tuberculosis, cardiovascular disease, ulcerative colitis). Within the order Primates, humans and apes appear uniquely susceptible to infectious and chronic conditions that are major illnesses in humans (i.e. Gram-negative bacterial sepsis, gonorrhea, particular cancers). I use a comparative immunological approach, including functional genetics/genomics, to explore the genetic and environmental underpinnings of population and species-specific immune function and disease manifestations. My overall goal is to contribute to a better understanding of 1) host-pathogen coevolution 2) genetic factors influencing human disease course 3) the effects of epidemics on human immune function variation and 4) the evolution of the order Primates. Address: www.jfbrinkworth.com
if you cannot find a paper listed here, please contact me for a pdf.
The local slaughterhouse’s coronavirus cluster was the first large outbreak we heard about in Cha... more The local slaughterhouse’s coronavirus cluster was the first large outbreak we heard about in Champaign County. The sprawling pork processing plant sits in the midst of cornfields some 17 miles north of the University of Illinois at Urbana-Champaign. Until early May, workers there processed 35 million pounds of pork a month. The company reported its first case on 25 April. Health inspectors arrived two days later to find the plant 90 percent out of compliance in its infection control practices. By 15 May, after testing 200 of the 627 workers for COVID-19, 83 got positive results. Management admitted it was ‘complex’ to track employees being tested and to follow up with those who had to be quarantined. That’s when they contacted the University of Illinois at Urbana-Champaign. They then announced confidently to the local press: We’ve got it under control. We have the scientists now.
The COVID-19 pandemic is extraordinary, but many ordinary events have contributed to its becoming... more The COVID-19 pandemic is extraordinary, but many ordinary events have contributed to its becoming and persistence. Here, we argue that the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, which has radically altered day-to-day life for people across the globe, was an inevitability of contemporary human ecology, presaged by spillovers past. We show the ways in which the emergence of this virus reiterates other infectious disease crises, from its origin via habitat encroachment and animal use by humans to its evolution of troublesome features, and we spotlight a long-running crisis of inequitable infectious disease incidence and death. We conclude by describing aspects of SARS-CoV-2 and the COVID-19 pandemic that present opportunities for disease control: spaces for intervention in infection and recovery that reduce transmission and impact. There are no more “before times”; therefore, we encourage embracing a future using old mitigation tactics and ...
Despite continued transmission of SARS-CoV-2 and sustained recommendations to wear protective fac... more Despite continued transmission of SARS-CoV-2 and sustained recommendations to wear protective face coverings, many people remained reluctant to comply throughout the early months of the pandemic. In the present study we surveyed an international cohort of participants on three different occasions from July to August, 2020 (N = 695) to examine the relative contribution of several factors in explaining variation in mask wearing behavior across a range of routine and leisure activities. We examine the role of COVID-19 prevalence, perceived risk of infection, COVID-19 related stress, demographics, time orientation, and several mask wearing attitudes and intentions. We find that COVID-19-related stress and the intention to protect oneself were reliably associated with more mask wearing across contexts, while other factors, such as anxiety caused by others’ mask wearing and the intention to wear masks to protect others, were context dependent. We discuss potential avenues for future resea...
That many women leave science somewhere between undergraduate studies and senior scientist positi... more That many women leave science somewhere between undergraduate studies and senior scientist positions has been well noted. Honest discussion of the challenges women face within and outside the STEM ...
Evolutionary Anthropology: Issues, News, and Reviews, 2021
Among mammals, humans are exquisitely sensitive to lipopolysaccharide (LPS), an environmentally p... more Among mammals, humans are exquisitely sensitive to lipopolysaccharide (LPS), an environmentally pervasive bacterial cell membrane component. Very small doses of LPS trigger powerful immune responses in humans and can even initiate symptoms of sepsis. Close evolutionary relatives such as African and Asian monkeys require doses that are an order of magnitude higher to do the same. Why humans have evolved such an energetically expensive antimicrobial strategy is a question that biological anthropologists are positioned to help address. Here we compare LPS sensitivity in primate/mammalian models and propose that human high sensitivity to LPS is adaptive, linked to multiple immune tactics against pathogens, and part of multi‐faceted anti‐microbial strategy that strongly overlaps with that of other mammals. We support a notion that LPS sensitivity in humans has been driven by microorganisms that constitutively live on us, and has been informed by human behavioral changes over our species' evolution (e.g., meat eating, agricultural practices, and smoking).
Objective. Since the COVID-19 pandemic began, wearing protective facial masks has become a divisi... more Objective. Since the COVID-19 pandemic began, wearing protective facial masks has become a divisive issue. Yet little is known about what drives individual differences in mask wearing. Methods and Measures. Here we surveyed an international cohort of participants (N = 753), about their use of masks and other variables related to mask wearing over three periods from July-August, 2020. Results. We found that greater prevalence of COVID-19, higher perceived risk of infection, stress, and future orientation predicted more frequent use of masks. Future-oriented people also experienced greater stress and reported higher perceived risk of infection. Conclusion. Results indicate that perceived risk of infection, stress, and future orientation reliably accounted for variation in reported mask-wearing behavior, but individual differences in mask-wearing intentions (e.g., protect self vs. others), and intergroup relations (e.g., political affiliation) should be considered in future investigati...
Despite their close genetic relatedness, apes and African and Asian monkeys (AAMs), strongly diff... more Despite their close genetic relatedness, apes and African and Asian monkeys (AAMs), strongly differ in their susceptibility to severe bacterial and viral infections that are important causes of human disease. Such differences between humans and other primates are thought to be a result, at least in part, of inter-species differences in immune response to infection. However, due to the lack of comparative functional data across species, it remains unclear in what ways the immune systems of humans and other primates differ. Here, we report the whole genome transcriptomic responses of ape species (human, common chimpanzee) and AAMs (rhesus macaque and olive baboon) to bacterial and viral stimulation. We find stark differences in the responsiveness of these groups, with apes mounting a markedly stronger early transcriptional response to both viral and bacterial stimulation, altering the transcription of ∼40% more genes than AAMs. Additionally, we find that genes involved in the regulati...
Here, we present a mechanistically grounded theory detailing a novel function of the behavioral i... more Here, we present a mechanistically grounded theory detailing a novel function of the behavioral immune system (BIS), the psychological system that prompts pathogen avoidance behaviors. We propose that BIS activity allows the body to downregulate basal inflammation, preventing resultant oxidative damage to DNA and promoting longevity. Study 1 investigated the relationship between a trait measure of pathogen avoidance motivation and in vitro and in vivo proinflammatory cytokine production. Study 2 examined the relationship between this same predictor and DNA damage often associated with prolonged inflammation. Results revealed that greater trait pathogen avoidance motivation predicts a) lower levels of spontaneous (but not stimulated) proinflammatory cytokine release by peripheral blood mononuclear cells (PBMCs), b) lower plasma levels of the proinflammatory cytokine interleukin-6 (IL-6), and c) lower levels of oxidative DNA damage. Thus, the BIS may promote health by protecting the b...
Status alters immune function in macaques Rhesus macaques experience variable levels of stress on... more Status alters immune function in macaques Rhesus macaques experience variable levels of stress on the basis of their position in the social hierarchy. To examine how stress affects immune function, Snyder-Mackler et al. manipulated the social status of individual macaques (see the Perspective by Sapolsky). Social status influenced the immune system at multiple levels, from immune cell numbers to gene expression, and altered signaling pathways in a model of response to infection. Macaques possess a plastic and adaptive immune response wherein social subordination promotes antibacterial responses, whereas high social status promotes antiviral responses. Science , this issue p. 1041 ; see also p. 967
The contribution of pre-mRNA processing mechanisms to the regulation of immune responses remains ... more The contribution of pre-mRNA processing mechanisms to the regulation of immune responses remains poorly studied despite emerging examples of their role as regulators of immune defenses. Here, we used mRNA sequencing to quantify gene expression and isoform abundances in primary macrophages from 60 individuals, before and after infection with two live bacteria. In response to both bacteria we identified thousands of genes that significantly change isoform usage in response to infection, and found global shifts towards (i) the inclusion of cassette exons and (ii) shorter 3' UTRs. Using complementary data collected in non-human primates, we show that these features are evolutionarily conserved among primates. Finally, our results suggest that the pervasive usage of shorter 3' UTRs is a mechanism for particular genes to evade repression by immune-activated miRNAs. Collectively, our results show that dynamic changes in RNA processing play a key role in the regulation of innate imm...
Toll-like receptors (TLRs) are an important interface between vertebrate hosts and pathogens. Fro... more Toll-like receptors (TLRs) are an important interface between vertebrate hosts and pathogens. From an evolutionary standpoint, these germline encoded receptors and their associated signaling pathways are interesting because they provide a window through which we can examine the relationships between primate environments, genomes, and immune responses. TLRs are key in host recognition of nonself and the activation of the innate immune response, a major determinant of host infection susceptibility and disease progression. TLR-initiated cell signaling not only forms an important part of host’s first line of defense against immune insult but also modulates adaptive immune responses. The efficacy of TLR-triggered immune responses has profound effects on host survival, with both overt and weak responses linked to host death. Despite sharing high genomic identity, primate species often manifest TLR-detected infectious pathogens differently (e.g., immunodeficiency viruses, Trypanosoma brucei, and Gram-negative bacteria). These differences suggest that primate TLR-triggered responses have diverged over time. In this chapter we review what is currently known about Toll-like receptor function and evolution in primates and discuss how studying the evolution of TLR-triggered immune responses may help explain disparities observed in microorganism-induced primate disease.
Chronic inflammatory and autoimmune diseases have been the focus of many genome-wide association ... more Chronic inflammatory and autoimmune diseases have been the focus of many genome-wide association studies (GWAS) because they represent a significant cause of illness and morbidity, and many are heritable. Almost a decade of GWAS studies suggests that the pathological inflammation associated with these diseases is controlled by a limited number of networked immune system genes. Chronic inflammatory and autoimmune diseases are enigmatic from an evolutionary perspective because they exert a negative affect on reproductive fitness. The persistence of these conditions may be partially explained by the important roles the implicated immune genes play in pathogen defense and other functions thought to be under strong natural selection in humans. The evolutionary reasons for chronic inflammatory and autoimmune disease persistence and uneven distribution across populations are the focus of this review.
The local slaughterhouse’s coronavirus cluster was the first large outbreak we heard about in Cha... more The local slaughterhouse’s coronavirus cluster was the first large outbreak we heard about in Champaign County. The sprawling pork processing plant sits in the midst of cornfields some 17 miles north of the University of Illinois at Urbana-Champaign. Until early May, workers there processed 35 million pounds of pork a month. The company reported its first case on 25 April. Health inspectors arrived two days later to find the plant 90 percent out of compliance in its infection control practices. By 15 May, after testing 200 of the 627 workers for COVID-19, 83 got positive results. Management admitted it was ‘complex’ to track employees being tested and to follow up with those who had to be quarantined. That’s when they contacted the University of Illinois at Urbana-Champaign. They then announced confidently to the local press: We’ve got it under control. We have the scientists now.
The COVID-19 pandemic is extraordinary, but many ordinary events have contributed to its becoming... more The COVID-19 pandemic is extraordinary, but many ordinary events have contributed to its becoming and persistence. Here, we argue that the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, which has radically altered day-to-day life for people across the globe, was an inevitability of contemporary human ecology, presaged by spillovers past. We show the ways in which the emergence of this virus reiterates other infectious disease crises, from its origin via habitat encroachment and animal use by humans to its evolution of troublesome features, and we spotlight a long-running crisis of inequitable infectious disease incidence and death. We conclude by describing aspects of SARS-CoV-2 and the COVID-19 pandemic that present opportunities for disease control: spaces for intervention in infection and recovery that reduce transmission and impact. There are no more “before times”; therefore, we encourage embracing a future using old mitigation tactics and ...
Despite continued transmission of SARS-CoV-2 and sustained recommendations to wear protective fac... more Despite continued transmission of SARS-CoV-2 and sustained recommendations to wear protective face coverings, many people remained reluctant to comply throughout the early months of the pandemic. In the present study we surveyed an international cohort of participants on three different occasions from July to August, 2020 (N = 695) to examine the relative contribution of several factors in explaining variation in mask wearing behavior across a range of routine and leisure activities. We examine the role of COVID-19 prevalence, perceived risk of infection, COVID-19 related stress, demographics, time orientation, and several mask wearing attitudes and intentions. We find that COVID-19-related stress and the intention to protect oneself were reliably associated with more mask wearing across contexts, while other factors, such as anxiety caused by others’ mask wearing and the intention to wear masks to protect others, were context dependent. We discuss potential avenues for future resea...
That many women leave science somewhere between undergraduate studies and senior scientist positi... more That many women leave science somewhere between undergraduate studies and senior scientist positions has been well noted. Honest discussion of the challenges women face within and outside the STEM ...
Evolutionary Anthropology: Issues, News, and Reviews, 2021
Among mammals, humans are exquisitely sensitive to lipopolysaccharide (LPS), an environmentally p... more Among mammals, humans are exquisitely sensitive to lipopolysaccharide (LPS), an environmentally pervasive bacterial cell membrane component. Very small doses of LPS trigger powerful immune responses in humans and can even initiate symptoms of sepsis. Close evolutionary relatives such as African and Asian monkeys require doses that are an order of magnitude higher to do the same. Why humans have evolved such an energetically expensive antimicrobial strategy is a question that biological anthropologists are positioned to help address. Here we compare LPS sensitivity in primate/mammalian models and propose that human high sensitivity to LPS is adaptive, linked to multiple immune tactics against pathogens, and part of multi‐faceted anti‐microbial strategy that strongly overlaps with that of other mammals. We support a notion that LPS sensitivity in humans has been driven by microorganisms that constitutively live on us, and has been informed by human behavioral changes over our species' evolution (e.g., meat eating, agricultural practices, and smoking).
Objective. Since the COVID-19 pandemic began, wearing protective facial masks has become a divisi... more Objective. Since the COVID-19 pandemic began, wearing protective facial masks has become a divisive issue. Yet little is known about what drives individual differences in mask wearing. Methods and Measures. Here we surveyed an international cohort of participants (N = 753), about their use of masks and other variables related to mask wearing over three periods from July-August, 2020. Results. We found that greater prevalence of COVID-19, higher perceived risk of infection, stress, and future orientation predicted more frequent use of masks. Future-oriented people also experienced greater stress and reported higher perceived risk of infection. Conclusion. Results indicate that perceived risk of infection, stress, and future orientation reliably accounted for variation in reported mask-wearing behavior, but individual differences in mask-wearing intentions (e.g., protect self vs. others), and intergroup relations (e.g., political affiliation) should be considered in future investigati...
Despite their close genetic relatedness, apes and African and Asian monkeys (AAMs), strongly diff... more Despite their close genetic relatedness, apes and African and Asian monkeys (AAMs), strongly differ in their susceptibility to severe bacterial and viral infections that are important causes of human disease. Such differences between humans and other primates are thought to be a result, at least in part, of inter-species differences in immune response to infection. However, due to the lack of comparative functional data across species, it remains unclear in what ways the immune systems of humans and other primates differ. Here, we report the whole genome transcriptomic responses of ape species (human, common chimpanzee) and AAMs (rhesus macaque and olive baboon) to bacterial and viral stimulation. We find stark differences in the responsiveness of these groups, with apes mounting a markedly stronger early transcriptional response to both viral and bacterial stimulation, altering the transcription of ∼40% more genes than AAMs. Additionally, we find that genes involved in the regulati...
Here, we present a mechanistically grounded theory detailing a novel function of the behavioral i... more Here, we present a mechanistically grounded theory detailing a novel function of the behavioral immune system (BIS), the psychological system that prompts pathogen avoidance behaviors. We propose that BIS activity allows the body to downregulate basal inflammation, preventing resultant oxidative damage to DNA and promoting longevity. Study 1 investigated the relationship between a trait measure of pathogen avoidance motivation and in vitro and in vivo proinflammatory cytokine production. Study 2 examined the relationship between this same predictor and DNA damage often associated with prolonged inflammation. Results revealed that greater trait pathogen avoidance motivation predicts a) lower levels of spontaneous (but not stimulated) proinflammatory cytokine release by peripheral blood mononuclear cells (PBMCs), b) lower plasma levels of the proinflammatory cytokine interleukin-6 (IL-6), and c) lower levels of oxidative DNA damage. Thus, the BIS may promote health by protecting the b...
Status alters immune function in macaques Rhesus macaques experience variable levels of stress on... more Status alters immune function in macaques Rhesus macaques experience variable levels of stress on the basis of their position in the social hierarchy. To examine how stress affects immune function, Snyder-Mackler et al. manipulated the social status of individual macaques (see the Perspective by Sapolsky). Social status influenced the immune system at multiple levels, from immune cell numbers to gene expression, and altered signaling pathways in a model of response to infection. Macaques possess a plastic and adaptive immune response wherein social subordination promotes antibacterial responses, whereas high social status promotes antiviral responses. Science , this issue p. 1041 ; see also p. 967
The contribution of pre-mRNA processing mechanisms to the regulation of immune responses remains ... more The contribution of pre-mRNA processing mechanisms to the regulation of immune responses remains poorly studied despite emerging examples of their role as regulators of immune defenses. Here, we used mRNA sequencing to quantify gene expression and isoform abundances in primary macrophages from 60 individuals, before and after infection with two live bacteria. In response to both bacteria we identified thousands of genes that significantly change isoform usage in response to infection, and found global shifts towards (i) the inclusion of cassette exons and (ii) shorter 3' UTRs. Using complementary data collected in non-human primates, we show that these features are evolutionarily conserved among primates. Finally, our results suggest that the pervasive usage of shorter 3' UTRs is a mechanism for particular genes to evade repression by immune-activated miRNAs. Collectively, our results show that dynamic changes in RNA processing play a key role in the regulation of innate imm...
Toll-like receptors (TLRs) are an important interface between vertebrate hosts and pathogens. Fro... more Toll-like receptors (TLRs) are an important interface between vertebrate hosts and pathogens. From an evolutionary standpoint, these germline encoded receptors and their associated signaling pathways are interesting because they provide a window through which we can examine the relationships between primate environments, genomes, and immune responses. TLRs are key in host recognition of nonself and the activation of the innate immune response, a major determinant of host infection susceptibility and disease progression. TLR-initiated cell signaling not only forms an important part of host’s first line of defense against immune insult but also modulates adaptive immune responses. The efficacy of TLR-triggered immune responses has profound effects on host survival, with both overt and weak responses linked to host death. Despite sharing high genomic identity, primate species often manifest TLR-detected infectious pathogens differently (e.g., immunodeficiency viruses, Trypanosoma brucei, and Gram-negative bacteria). These differences suggest that primate TLR-triggered responses have diverged over time. In this chapter we review what is currently known about Toll-like receptor function and evolution in primates and discuss how studying the evolution of TLR-triggered immune responses may help explain disparities observed in microorganism-induced primate disease.
Chronic inflammatory and autoimmune diseases have been the focus of many genome-wide association ... more Chronic inflammatory and autoimmune diseases have been the focus of many genome-wide association studies (GWAS) because they represent a significant cause of illness and morbidity, and many are heritable. Almost a decade of GWAS studies suggests that the pathological inflammation associated with these diseases is controlled by a limited number of networked immune system genes. Chronic inflammatory and autoimmune diseases are enigmatic from an evolutionary perspective because they exert a negative affect on reproductive fitness. The persistence of these conditions may be partially explained by the important roles the implicated immune genes play in pathogen defense and other functions thought to be under strong natural selection in humans. The evolutionary reasons for chronic inflammatory and autoimmune disease persistence and uneven distribution across populations are the focus of this review.
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Papers by Jessica Brinkworth