Infectious and lifestyle modifiers of immunity and host resilience

Bajpai, Geetika; Nahrendorf, Matthias

doi:10.1016/j.immuni.2021.05.011

Cited by 13 publications

(9 citation statements)

References 141 publications

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“…Many additional factors (previous infections, vaccination, physical activities, stress) which are not considered here also have an impact on trained immunity (118) and the activation status of macrophages. While the difficulty to assess and describe the contribution of these non-heritable, environmental factors on inflammation in general and gout in particular, poses a real challenge, the possibility to change them, as opposed to heritable features, makes their identification an exciting field of research and a promising preventive/therapeutic opportunity.…”

Section: Discussionmentioning

confidence: 99%

Where Epigenetics Meets Food Intake: Their Interaction in the Development/Severity of Gout and Therapeutic Perspectives

Georgel

2021

Front. Immunol.

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Gout is the most frequent form of inflammatory arthritis in the world. Its prevalence is particularly elevated in specific geographical areas such as in the Oceania/Pacific region and is rising in the US, Europe, and Asia. Gout is a severe and painful disease, in which co-morbidities are responsible for a significant reduction in life expectancy. However, gout patients remain ostracized because the disease is still considered “self-inflicted”, as a result of unhealthy lifestyle and excessive food and alcohol intake. While the etiology of gout flares is clearly associated with the presence of monosodium urate (MSU) crystal deposits, several major questions remain unanswered, such as the relationships between diet, hyperuricemia and gout flares or the mechanisms by which urate induces inflammation. Recent advances have identified gene variants associated with gout incidence. Nevertheless, genetic origins of gout combined to diet-related possible uric acid overproduction account for the symptoms in only a minor portion of patients. Hence, additional factors must be at play. Here, we review the impact of epigenetic mechanisms in which nutrients (such as ω-3 polyunsaturated fatty acids) and/or dietary-derived metabolites (like urate) trigger anti/pro-inflammatory responses that may participate in gout pathogenesis and severity. We propose that simple dietary regimens may be beneficial to complement therapeutic management or contribute to the prevention of flares in gout patients.

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Section: Discussionmentioning

confidence: 99%

Where Epigenetics Meets Food Intake: Their Interaction in the Development/Severity of Gout and Therapeutic Perspectives

Georgel

2021

Front. Immunol.

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“…Biobank data revealed that individuals with rare CD36 LoF variants have higher prevalence of Lyme disease regardless of the genetic diversity and variability among a large population in Bio Me ( 46 ). Our findings were achieved despite the multifactorial and polygenic nature of immune traits ( 57 ) and distinctive non-heritable factors, such as physical activity, prior infections, diet, vaccination status and psychosocial stress ( 58 ). Although striking, our results have some limitations.…”

Section: Discussionmentioning

confidence: 73%

CD36 homologs determine microbial resistance to the Lyme disease spirochete

O’Neal

Singh

Forrest

et al. 2022

Preprint

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Pattern recognition receptors sense pathogens in arthropods and mammals through distinct immune processes. Whether these molecules share a similar function and recognize the same microbe in evolutionarily distant species remain ill-defined. Here, we establish that the CD36 superfamily is required for Borrelia burgdorferi resistance in both the arthropod vector and humans. Using the blacklegged tick Ixodes scapularis and an electronic health record-linked biobank, we demonstrate that CD36 members elicit immunity to the Lyme disease spirochete. In ticks, the CD36-like protein Croquemort recognizes lipids and initiates the immune deficiency and jun N-terminal kinase pathways against B. burgdorferi. In humans, exome sequencing and clinical information reveal that individuals with CD36 loss-of-function variants have increased prevalence of Lyme disease. Altogether, we discovered a conserved mechanism of anti-bacterial immunity.

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“…In addition to infectious disease exposure, there is an increasing awareness of the influence of non-infectious/lifestyle modifiers of trained immunity ( Furman et al, 2019 ; Bajpai and Nahrendorf, 2021 ). For example, stress induced noradrenaline may induce proinflammatory biased functional and epigenetic changes in myeloid cells ( van der Heijden et al, 2020 ).…”

Section: What Is Trained Immunity and Why Might It Be Relevant To Lon...mentioning

confidence: 99%

Does the trained immune system play an important role in the extreme longevity that is seen in the Sardinian blue zone?

Soloski¹,

Poulain²,

Pes³

2022

Front. Aging

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Villages in the island of Sardinia in the Mediterranean that display exceptional longevity are clustered within a defined mountainous region. Because of their unique location we hypothesize that these villages had a unique infectious disease exposure relevant to the observed successful longevity. These highland villages had a significant exposure to malaria in the first half of the 20th century after which malaria was eliminated due to vector control mechanisms. In addition, there is likely a high incidence of Helicobacter pylori infections among shepherds in Sardinia, the primary occupation of many living in the LBZ, as well as helminth infections among children. This suggests that individuals living in the LBZ had a unique infectious disease exposure. Specifically, we hypothesize that the continued high exposure of residents in the LBZ to these infectious agents prior to the 1950s lead to the generation of a uniquely trained (or imprinted) immune system. Once some of these diseases were eliminated in the latter half of the century, individuals within the LBZ were equipped with a trained immune system that was uniquely capable of not only responding effectively to common infections but also responding in a manner that maximized maintaining tissue health. In addition, there are lifestyle factors that also favor such a trained immune system. This hypothesis may help explain the slow progression of chronic immune mediated diseases as well as other chronic non-transmissible age-related diseases seen in the Sardinian LBZ and serve as a template for future studies that support or refute this hypothesis.

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Infectious and lifestyle modifiers of immunity and host resilience

Cited by 13 publications

References 141 publications

Where Epigenetics Meets Food Intake: Their Interaction in the Development/Severity of Gout and Therapeutic Perspectives

Where Epigenetics Meets Food Intake: Their Interaction in the Development/Severity of Gout and Therapeutic Perspectives

CD36 homologs determine microbial resistance to the Lyme disease spirochete

Does the trained immune system play an important role in the extreme longevity that is seen in the Sardinian blue zone?

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