Sepsis and the evolution of human increased sensitivity to lipopolysaccharide

Brinkworth, Jessica F.; Valizadegan, Negin

doi:10.1002/evan.21887

Cited by 15 publications

(16 citation statements)

References 182 publications

(227 reference statements)

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“…At the species level, many more human genes were differentially upregulated in response to LPS than in the other three species, consistent with evidence reviewed by Brinkworth & Valizadegan (2021). Humans also exhibited markedly upregulated interferon gamma (IFN-𝛾) and the canonical T-cell costimulatory molecule CD80, which Hawash et al (2021) speculate might mediate more effective killing of viral and bacterial pathogens compared to the other species.…”

Section: Divergent Immune Responses To Bacterial and Viral Stimulisupporting

confidence: 75%

“…Mammals have multiple mechanisms to detect lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, which then activate further energy intensive mechanisms, involving upregulation of thousands of genes, that sequester and eliminate the bacteria. Brinkworth & Valizadegan (2021) review the evidence that, compared to most other mammals, the human immune system is highly sensitive to LPS, mounting a robust immune response to quantities about 1/10 of those needed to activate similar responses in other species. Brinkworth & Valizadegan (2021) attribute human's increased LPS sensitivity, in part, to increased exposure to microorganisms from increased butchering and eating of meat in early Homo, as does a study that links human sensitivity to LPS to the loss-of-function mutation in CMAH .…”

Section: Divergent Immune Responses To Bacterial and Viral Stimulimentioning

confidence: 99%

“…Brinkworth & Valizadegan (2021) review the evidence that, compared to most other mammals, the human immune system is highly sensitive to LPS, mounting a robust immune response to quantities about 1/10 of those needed to activate similar responses in other species. Brinkworth & Valizadegan (2021) attribute human's increased LPS sensitivity, in part, to increased exposure to microorganisms from increased butchering and eating of meat in early Homo, as does a study that links human sensitivity to LPS to the loss-of-function mutation in CMAH . Hawash et al (2021) investigated innate immune responses to LPS, a bacteria mimic, and gardiquimod (GARD), a viral mimic, in four primate species: humans and chimpanzees (apes) and rhesus macaques and olive baboons (African and Asian monkeys).…”

Section: Divergent Immune Responses To Bacterial and Viral Stimulimentioning

confidence: 99%

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Homo medicus: The transition to meat eating, increased pathogen pressure, and the constitutive and inducible use of pharmacological plants in Homo

Hagen¹,

Blackwell²,

Lightner³

et al. 2021

Preprint

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The human lineage entered a more carnivorous niche 2.6 mya. A range of evidence indicates this increased zoonotic pathogen pressure. This evidence includes increased zoonotic infections modern hunter-gatherers and bushmeat hunters relative to others living in the same environments, exceptionally low stomach pH compared to other primates, human-specific downregulation in ANTXR2 that would have protected against increased exposure to zoonotic anthrax, exceptional human immune responses to LPS compared to other primates, and other divergent immune genes. These all point to change, and likely intensification, in the disease environment of Homo compared to earlier hominins and other apes. At the same time, the brain, an organ in which inflammatory immune responses are highly constrained, begins to increase, eventually tripling in size. We propose that the combination of increased zoonotic pathogen pressure and the challenges of defending a large brain and body from pathogens across what would eventually become the longest lifespan of any mammal, selected for intensification of the self-medication strategies already in place in apes and other primates, resulting in a variety of plant-based pathogen defenses. In support, there is evidence of medicinal plant use by hominins in the middle Paleolithic, and all cultures today have sophisticated, plant-based medical systems, incorporate plant components high in secondary compounds (spices) into food, and regularly consume psychoactive substances that are harmful to helminths and other pathogens in the CNS and other tissues. The computational challenges of discovering effective plant-based treatments, and the economic challenges of benefiting from costly-to- acquire medical knowledge that would be more often useful to others than oneself, were selection pressures for increased cognitive abilities and unique exchange relationships in Homo. In the story of human evolution, which has long featured hunters, shamans and healers had an equal role to play.

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Section: Divergent Immune Responses To Bacterial and Viral Stimulisupporting

confidence: 75%

Section: Divergent Immune Responses To Bacterial and Viral Stimulimentioning

confidence: 99%

Section: Divergent Immune Responses To Bacterial and Viral Stimulimentioning

confidence: 99%

See 1 more Smart Citation

Homo medicus: The transition to meat eating, increased pathogen pressure, and the constitutive and inducible use of pharmacological plants in Homo

Hagen¹,

Blackwell²,

Lightner³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Atherosclerosis is an inflammatory process of the artery that leads to cholesterol accumulation and cardiovascular disease. We hypothesized that LPS may help to explain accelerated atherosclerosis, and the reason for this is threefold: (1) LPS binds to lipoproteins for its elimination; therefore, lipoproteins located in the subendothelial space may contain LPS; (2) unlike most mammals, humans have developed a very high immunomodulatory response to LPS linked to the acyl chains of lipid A [ 27 ]; (3) LPS has been found in the carotid plaques of patients with atherosclerosis [ 28 ]. Therefore, an exacerbated immune response leading to foam cell formation may be triggered by LPS even at similar concentrations of circulating cholesterol.…”

Section: Discussionmentioning

confidence: 99%

“…As mentioned above, humans are much more sensitive to LPS than other mammals, and very low amounts of LPS can cause inflammation and elicit an immune response [ 27 ]. As this immune response is mostly due to acyl chains, in our study, we also measured the distribution acyl chains in each lipoprotein.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the LPS and 3OHFA Contents in the Lipoprotein Fractions and Lipoprotein Particles of Healthy Men

et al. 2021

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Atherosclerosis is a chronic inflammatory disease that is caused by the accumulation of LDL particles in the intima, causing the activation of immune cells and triggering an inflammatory response. LPS is a potent activator of the innate immune response and it can be transported by lipoproteins. Since humans are much more sensitive to LPS than other mammals, and very low amounts of LPS can elicit an immune response, the aim of this study is to characterize the distribution of LPS and its immunogenic portion (3OHFAs) among lipoprotein types of healthy men. We separated lipoprotein fractions by ultracentrifugation and the amount of each 3OHFA was measured by MS in each lipoprotein fraction to calculate LPS concentration. Lipoprotein particle concentration was measured by NMR. LDL and HDL fractions transported the highest concentration of LPS (35.7% and 31.5%, respectively), but VLDL particles carried more LPS molecules per particle (0.55 molecules/particle) than LDL or HDL (p < 0.01). The distribution of LPS and all 3OHFAs among lipoprotein fractions showed high interindividual variability, suggesting that they may be studied as a potential biomarker. This may help understand the role of LPS in atherosclerosis in those cases where the disease cannot be explained by traditional risk factors.

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On race, human variation, and who gets and dies of sepsis

Brinkworth

Shaw

2022

American Journal of Biological Anthropology

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COVID‐19 has highlighted a brutal reality known for decades, that Black, Indigenous, and People of Color bear a disproportionate burden of US annual sepsis cases. While plentiful research funds have been spent investigating genetic reasons for racial disparities in sepsis, an abundance of research shows that sepsis incidence and mortality maps to indicators of colonial practices including residential segregation, economic and marginalization sepsis, and denial of care. Here we argue that sepsis risk is an immunological embodiment of racism in colonial states, that the factors contributing to sepsis disparities are insidious and systemic. We show that regardless of causative pathogen, or host ancestry, racialized people get and die of sepsis most frequently in a pattern repeatedly reiterated worldwide. Lastly, we argue that while alleviation of sepsis disparities requires radical, multiscale intervention, biological anthropologists have a responsibility in this crisis. While some of us can harness our expertise to take on the ground action in sepsis prevention, all of us can leverage our positions as the first point of contact for in depth human biology instruction on most college campuses. As a leading cause of death worldwide, and a syndrome that exhibits the interplay between human physiology, race and environment, sepsis is at the nexus of major themes in biological anthropology and is a natural fit for the field's curriculum. In adopting a discussion of race and sepsis in our courses, we not only develop new research areas but increase public awareness of both sepsis and the factors contributing to uneven sepsis burden.

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Sepsis and the evolution of human increased sensitivity to lipopolysaccharide

Cited by 15 publications

References 182 publications

Homo medicus: The transition to meat eating, increased pathogen pressure, and the constitutive and inducible use of pharmacological plants in Homo

Homo medicus: The transition to meat eating, increased pathogen pressure, and the constitutive and inducible use of pharmacological plants in Homo

Characterization of the LPS and 3OHFA Contents in the Lipoprotein Fractions and Lipoprotein Particles of Healthy Men

On race, human variation, and who gets and dies of sepsis

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