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Erschienen in: Archivum Immunologiae et Therapiae Experimentalis 1/2022

01.12.2022 | Original Article

Sex Differences in Innate Immune Response of Peripheral Blood Leukocytes of Alzheimer’s Disease Patients

verfasst von: Marta Sochocka, Michał Ochnik, Maciej Sobczyński, Beata Orzechowska, Jerzy Leszek

Erschienen in: Archivum Immunologiae et Therapiae Experimentalis | Ausgabe 1/2022

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Abstract

Neurodegenerative disorders, including Alzheimer’s disease (AD), are associated with a disruption of normal immune function that could potentially impact the brain. In AD sex and gender have been noted as relevant to disease prevalence or clinical manifestation. It is suggested that disease progression could vary as a result of the different inflammation state among males and females. The objective was to investigate sex-dependent difference in innate immunity of AD patients and healthy, age-matched controls. The level of innate immunity was measured with test based on peripheral blood leukocytes (PBLs) resistance to viral infection (vesicular stomatitis virus, VSV) ex vivo. Cytokine: TNF-α, IFN-γ, IL-1β, IL-10 production by uninfected and VSV-infected PBLs ex vivo with enzyme-linked immunosorbent assay were examined. In contrast to controls, women with AD exhibit lower average level of innate immunity than AD men. The mean level of TNF-α, IL-10 and IL-1β was higher in AD men than in AD women whereas such changes were not observed among controls. The level of IFN-γ was higher in AD than in controls. PBLs from AD did not increase IFN-γ production after viral infection in contrast to controls. Leukocytes from women with AD exhibited a weaker response to viral infection and much less cytokine production compared to men with AD. It is important to consider sex as a biological variable in AD as it shows promises to advance our understanding of mechanisms of AD pathology and may be the basis for future treatment of AD.
Literatur
Zurück zum Zitat Arosio B, D’Addario C, Gussago C et al (2014) Peripheral blood mononuclear cells as a laboratory to study dementia in the elderly. BioMed Res Int 2014:169203 PubMedPubMedCentralCrossRef Arosio B, D’Addario C, Gussago C et al (2014) Peripheral blood mononuclear cells as a laboratory to study dementia in the elderly. BioMed Res Int 2014:169203 PubMedPubMedCentralCrossRef
Zurück zum Zitat Bektas A, Schurman SH, Sen R et al (2018) Aging, inflammation and the environment. Exp Gerontol 105:10–18 PubMedCrossRef Bektas A, Schurman SH, Sen R et al (2018) Aging, inflammation and the environment. Exp Gerontol 105:10–18 PubMedCrossRef
Zurück zum Zitat Bettcher BM, Tansey MG, Dorothée G et al (2021) Peripheral and central immune system crosstalk in Alzheimer disease—a research prospectus. Nat Rev Neurol 17:689–701 PubMedPubMedCentralCrossRef Bettcher BM, Tansey MG, Dorothée G et al (2021) Peripheral and central immune system crosstalk in Alzheimer disease—a research prospectus. Nat Rev Neurol 17:689–701 PubMedPubMedCentralCrossRef
Zurück zum Zitat Butler L, Walker AK (2021) The role of chronic infection in alzheimer’s disease: instigators, co-conspirators, or bystanders? Curr Clin Microbiol Rep 8:199–212 PubMedCrossRef Butler L, Walker AK (2021) The role of chronic infection in alzheimer’s disease: instigators, co-conspirators, or bystanders? Curr Clin Microbiol Rep 8:199–212 PubMedCrossRef
Zurück zum Zitat Ciarambino T, Para O, Giordano M (2021) Immune system and COVID-19 by sex differences and age. Womens Health 17:17455065211022262 Ciarambino T, Para O, Giordano M (2021) Immune system and COVID-19 by sex differences and age. Womens Health 17:17455065211022262
Zurück zum Zitat Esteras N, Alquézar C, de la Encarnación A et al (2016) Lymphocytes in Alzheimer’s disease pathology: altered signaling pathways. Curr Alzheimer Res 13:439–449 PubMedCrossRef Esteras N, Alquézar C, de la Encarnación A et al (2016) Lymphocytes in Alzheimer’s disease pathology: altered signaling pathways. Curr Alzheimer Res 13:439–449 PubMedCrossRef
Zurück zum Zitat Ferretti MT, Iulita MF, Cavedo E et al (2018) Sex differences in Alzheimer disease—the gateway to precision medicine. Nat Rev Neurol 14:457–469 PubMedCrossRef Ferretti MT, Iulita MF, Cavedo E et al (2018) Sex differences in Alzheimer disease—the gateway to precision medicine. Nat Rev Neurol 14:457–469 PubMedCrossRef
Zurück zum Zitat Fuentes E, Fuentes M, Alarcón M et al (2017) Immune system dysfunction in the elderly. An Acad Bras Cienc 89:285–299 PubMedCrossRef Fuentes E, Fuentes M, Alarcón M et al (2017) Immune system dysfunction in the elderly. An Acad Bras Cienc 89:285–299 PubMedCrossRef
Zurück zum Zitat Hall JR, Wiechmann AR, Johnson LA et al (2013) Biomarkers of vascular risk, systemic inflammation, and microvascular pathology and neuropsychiatric symptoms in Alzheimer’s disease. J Alzheimers Dis 35:363–371 PubMedPubMedCentralCrossRef Hall JR, Wiechmann AR, Johnson LA et al (2013) Biomarkers of vascular risk, systemic inflammation, and microvascular pathology and neuropsychiatric symptoms in Alzheimer’s disease. J Alzheimers Dis 35:363–371 PubMedPubMedCentralCrossRef
Zurück zum Zitat Hanamsagar R, Bilbo SD (2016) Sex differences in neurodevelopmental and neurodegenerative disorders: focus on microglial function and neuroinflammation during development. J Steroid Biochem Mol Biol 160:127–133 PubMedCrossRef Hanamsagar R, Bilbo SD (2016) Sex differences in neurodevelopmental and neurodegenerative disorders: focus on microglial function and neuroinflammation during development. J Steroid Biochem Mol Biol 160:127–133 PubMedCrossRef
Zurück zum Zitat Imbimbo BP, Lozupone M, Watling M et al (2020) Discontinued disease-modifying therapies for Alzheimer’s disease: status and future perspectives. Expert Opin Investig Drugs 29:919–933 PubMedCrossRef Imbimbo BP, Lozupone M, Watling M et al (2020) Discontinued disease-modifying therapies for Alzheimer’s disease: status and future perspectives. Expert Opin Investig Drugs 29:919–933 PubMedCrossRef
Zurück zum Zitat Jabbari Azad F, Talaei A, Rafatpanah H et al (2014) Association between cytokine production and disease severity in Alzheimer’s disease. Iran J Allergy Asthma Immunol 13:433–439 PubMed Jabbari Azad F, Talaei A, Rafatpanah H et al (2014) Association between cytokine production and disease severity in Alzheimer’s disease. Iran J Allergy Asthma Immunol 13:433–439 PubMed
Zurück zum Zitat Jatczak B, Leszek J, Siemieniec I et al (2012) Age- and disease-related innate immunity of human leukocytes ex vivo. Exp Gerontol 47:8–13 PubMedCrossRef Jatczak B, Leszek J, Siemieniec I et al (2012) Age- and disease-related innate immunity of human leukocytes ex vivo. Exp Gerontol 47:8–13 PubMedCrossRef
Zurück zum Zitat Jevtic S, Sengar AS, Salter MW et al (2017) The role of the immune system in Alzheimer disease: etiology and treatment. Ageing Res Rev 40:84–94 PubMedCrossRef Jevtic S, Sengar AS, Salter MW et al (2017) The role of the immune system in Alzheimer disease: etiology and treatment. Ageing Res Rev 40:84–94 PubMedCrossRef
Zurück zum Zitat King E, O’Brien JT, Donaghy P et al (2018) Peripheral inflammation in prodromal Alzheimer’s and Lewy body dementias. J Neurol Neurosurg Psychiatry 89:339–345 PubMedCrossRef King E, O’Brien JT, Donaghy P et al (2018) Peripheral inflammation in prodromal Alzheimer’s and Lewy body dementias. J Neurol Neurosurg Psychiatry 89:339–345 PubMedCrossRef
Zurück zum Zitat Kinney JW, Bemiller SM, Murtishaw AS et al (2018) Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement 4:575–590 CrossRef Kinney JW, Bemiller SM, Murtishaw AS et al (2018) Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement 4:575–590 CrossRef
Zurück zum Zitat Klein SL, Flanagan KL (2016) Sex differences in immune responses. Nat Rev Immunol 16:626–638 PubMedCrossRef Klein SL, Flanagan KL (2016) Sex differences in immune responses. Nat Rev Immunol 16:626–638 PubMedCrossRef
Zurück zum Zitat Lai KSP, Liu CS, Rau A et al (2017) Peripheral inflammatory markers in Alzheimer’s disease: a systematic review and meta-analysis of 175 studies. J Neurol Neurosurg Psychiatry 88:876–882 PubMedCrossRef Lai KSP, Liu CS, Rau A et al (2017) Peripheral inflammatory markers in Alzheimer’s disease: a systematic review and meta-analysis of 175 studies. J Neurol Neurosurg Psychiatry 88:876–882 PubMedCrossRef
Zurück zum Zitat Lakens D (2013) Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Front Psychol 4:863 PubMedPubMedCentralCrossRef Lakens D (2013) Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Front Psychol 4:863 PubMedPubMedCentralCrossRef
Zurück zum Zitat Le Page A, Dupuis G, Frost EH et al (2018) Role of the peripheral innate immune system in the development of Alzheimer’s disease. Exp Gerontol 107:59–66 PubMedCrossRef Le Page A, Dupuis G, Frost EH et al (2018) Role of the peripheral innate immune system in the development of Alzheimer’s disease. Exp Gerontol 107:59–66 PubMedCrossRef
Zurück zum Zitat Lim A, Krajina K, Marsland AL (2013) Peripheral inflammation and cognitive aging. Mod Trends Pharmacopsychiatry 28:175–187 PubMedCrossRef Lim A, Krajina K, Marsland AL (2013) Peripheral inflammation and cognitive aging. Mod Trends Pharmacopsychiatry 28:175–187 PubMedCrossRef
Zurück zum Zitat Lopez-Lee C, Kodama L, Gan L (2021) Sex differences in neurodegeneration: the role of the immune system in humans. Biol Psychiatry 91:72–80 PubMedCrossRef Lopez-Lee C, Kodama L, Gan L (2021) Sex differences in neurodegeneration: the role of the immune system in humans. Biol Psychiatry 91:72–80 PubMedCrossRef
Zurück zum Zitat Martin M, Rehani K, Jope RS et al (2005) Toll-like receptor—mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol 6:777–784 PubMedPubMedCentralCrossRef Martin M, Rehani K, Jope RS et al (2005) Toll-like receptor—mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol 6:777–784 PubMedPubMedCentralCrossRef
Zurück zum Zitat Mastrangelo MA, Sudol KL, Narrow WC et al (2009) Interferon-{gamma} differentially affects Alzheimer’s disease pathologies and induces neurogenesis in triple transgenic-AD mice. Am J Pathol 175:2076–2088 PubMedPubMedCentralCrossRef Mastrangelo MA, Sudol KL, Narrow WC et al (2009) Interferon-{gamma} differentially affects Alzheimer’s disease pathologies and induces neurogenesis in triple transgenic-AD mice. Am J Pathol 175:2076–2088 PubMedPubMedCentralCrossRef
Zurück zum Zitat Nebel RA, Aggarwal NT, Barnes LL et al (2018) Understanding the impact of sex and gender in Alzheimer’s disease: a call to action. Alzheimers Dement 14:1171–1183 PubMedPubMedCentralCrossRef Nebel RA, Aggarwal NT, Barnes LL et al (2018) Understanding the impact of sex and gender in Alzheimer’s disease: a call to action. Alzheimers Dement 14:1171–1183 PubMedPubMedCentralCrossRef
Zurück zum Zitat Orzechowska B, Antoszków Z, Błach-Olszewska Z (2003) Individual differentiation of innate antiviral immunity in humans; the role of endogenous interferons and tumor necrosis factor in the immunity of leukocytes. Arch Immunol Ther Exp 51:51–60 Orzechowska B, Antoszków Z, Błach-Olszewska Z (2003) Individual differentiation of innate antiviral immunity in humans; the role of endogenous interferons and tumor necrosis factor in the immunity of leukocytes. Arch Immunol Ther Exp 51:51–60
Zurück zum Zitat Rosenthal R, Rosnow RL, Rubin DB (2000) Contrasts and effect sizes in behavioral research—a correlational approach. Cambridge University Press Rosenthal R, Rosnow RL, Rubin DB (2000) Contrasts and effect sizes in behavioral research—a correlational approach. Cambridge University Press
Zurück zum Zitat Rousseeuw PJ, Croux C (1993) Alternatives to the median absolute deviation. J Am Stat Assoc 88:1273–1283 CrossRef Rousseeuw PJ, Croux C (1993) Alternatives to the median absolute deviation. J Am Stat Assoc 88:1273–1283 CrossRef
Zurück zum Zitat Rybka K, Orzechowska B, Siemieniec I et al (2003) Age related natural antiviral non-specific immunity of human leukocytes. Med Sci Monit 9:BR413-417 PubMed Rybka K, Orzechowska B, Siemieniec I et al (2003) Age related natural antiviral non-specific immunity of human leukocytes. Med Sci Monit 9:BR413-417 PubMed
Zurück zum Zitat Sawilowsky SS (2009) New effect size rules of thumb. J Mod Appl Stat Methods 8(2): 597–599 CrossRef Sawilowsky SS (2009) New effect size rules of thumb. J Mod Appl Stat Methods 8(2): 597–599 CrossRef
Zurück zum Zitat Schwartz M, Deczkowska A (2016) Neurological disease as a failure of brain-immune crosstalk: the multiple faces of neuroinflammation. Trends Immunol 37:668–679 PubMedCrossRef Schwartz M, Deczkowska A (2016) Neurological disease as a failure of brain-immune crosstalk: the multiple faces of neuroinflammation. Trends Immunol 37:668–679 PubMedCrossRef
Zurück zum Zitat Sochocka M, Diniz BS, Leszek J (2017) Inflammatory response in the CNS: friend or foe? Mol Neurobiol 54:8071–8089 PubMedCrossRef Sochocka M, Diniz BS, Leszek J (2017) Inflammatory response in the CNS: friend or foe? Mol Neurobiol 54:8071–8089 PubMedCrossRef
Zurück zum Zitat Sochocka M, Ochnik M, Sobczyński M et al (2019) New therapeutic targeting of Alzheimer’s disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response—preliminary study. J Neuroinflammation 16:137 PubMedPubMedCentralCrossRef Sochocka M, Ochnik M, Sobczyński M et al (2019) New therapeutic targeting of Alzheimer’s disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response—preliminary study. J Neuroinflammation 16:137 PubMedPubMedCentralCrossRef
Zurück zum Zitat Su C, Zhao K, Xia H et al (2019) Peripheral inflammatory biomarkers in Alzheimer’s disease and mild cognitive impairment: a systematic review and meta-analysis. Psychogeriatrics 19:300–309 PubMedCrossRef Su C, Zhao K, Xia H et al (2019) Peripheral inflammatory biomarkers in Alzheimer’s disease and mild cognitive impairment: a systematic review and meta-analysis. Psychogeriatrics 19:300–309 PubMedCrossRef
Zurück zum Zitat Tomczyk T, Wróbel G, Chaber R et al (2018) Immune consequences of in vitro infection of human peripheral blood leukocytes with vesicular stomatitis virus. J Innate Immun 10:131–144 PubMedPubMedCentralCrossRef Tomczyk T, Wróbel G, Chaber R et al (2018) Immune consequences of in vitro infection of human peripheral blood leukocytes with vesicular stomatitis virus. J Innate Immun 10:131–144 PubMedPubMedCentralCrossRef
Zurück zum Zitat Zaczynska E, Duś D, Paprocka M et al (2008) Resistance of human leukocytes to vesicular stomatitis virus infection as one of the innate antiviral immune activities; participation of cell subpopulations. Folia Histochem Cytobiol 46:39–43 PubMedCrossRef Zaczynska E, Duś D, Paprocka M et al (2008) Resistance of human leukocytes to vesicular stomatitis virus infection as one of the innate antiviral immune activities; participation of cell subpopulations. Folia Histochem Cytobiol 46:39–43 PubMedCrossRef
Metadaten
Titel
Sex Differences in Innate Immune Response of Peripheral Blood Leukocytes of Alzheimer’s Disease Patients
verfasst von
Marta Sochocka
Michał Ochnik
Maciej Sobczyński
Beata Orzechowska
Jerzy Leszek
Publikationsdatum
01.12.2022
Verlag
Springer International Publishing
Erschienen in
Archivum Immunologiae et Therapiae Experimentalis / Ausgabe 1/2022
Print ISSN: 0004-069X
Elektronische ISSN: 1661-4917
DOI
https://doi.org/10.1007/s00005-022-00653-w

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