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  1. Article ; Online: Zone defence - the gut microbiota position macrophages for optimal liver protection.

    English, Kieran / Bowen, David G / Bertolino, Patrick

    Immunology and cell biology

    2021  Volume 99, Issue 6, Page(s) 565–569

    MeSH term(s) Gastrointestinal Microbiome ; Humans ; Liver ; Macrophages ; Non-alcoholic Fatty Liver Disease
    Language English
    Publishing date 2021-06-02
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1111/imcb.12476
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  2. Article ; Online: A hepatic network of dendritic cells mediates CD4 T cell help outside lymphoid organs.

    English, Kieran / Kwan, Rain / Holz, Lauren E / McGuffog, Claire / Krol, Jelte M M / Kempe, Daryan / Kaisho, Tsuneyasu / Heath, William R / Lisowski, Leszek / Biro, Maté / McCaughan, Geoffrey W / Bowen, David G / Bertolino, Patrick

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 1261

    Abstract: ... While ... ...

    Abstract While CD4
    MeSH term(s) Antigens ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Dendritic Cells/immunology ; Liver/immunology ; Humans ; Lymphoid Tissue/immunology
    Chemical Substances Antigens
    Language English
    Publishing date 2024-02-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45612-5
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  3. Article ; Online: Interleukin-22, interleukin-17, and other cytokines: a wall is coming down.

    Bertolino, Patrick

    Hepatology (Baltimore, Md.)

    2008  Volume 47, Issue 1, Page(s) 345–348

    Language English
    Publishing date 2008-01
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.22154
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  4. Article ; Online: Induction Phase of Spontaneous Liver Transplant Tolerance.

    McCaughan, Geoffrey W / Bowen, David G / Bertolino, Patrick J

    Frontiers in immunology

    2020  Volume 11, Page(s) 1908

    Abstract: The liver has long been known to possess tolerogenic properties. Early experiments in liver transplantation demonstrated that in animal models, hepatic allografts could be accepted across MHC-mismatch without the use of immunosuppression, and that ... ...

    Abstract The liver has long been known to possess tolerogenic properties. Early experiments in liver transplantation demonstrated that in animal models, hepatic allografts could be accepted across MHC-mismatch without the use of immunosuppression, and that transplantation of livers from the same donor was capable of inducing tolerance to other solid organs that would normally otherwise be rejected. Although this phenomenon is less pronounced in human liver transplantation, lower levels of immunosuppression are nevertheless required for graft acceptance than for other solid organs, and in a minority of individuals immunosuppression can be discontinued in the longer term. The mechanisms underlying this unique hepatic property have not yet been fully delineated, however it is clear that immunological events in the early period post-liver transplant are key to generation of hepatic allograft tolerance. Both the hepatic parenchyma and the large number of donor passenger leukocytes contained within the liver allograft have been demonstrated to contribute to the generation of donor-specific tolerance in the early post-transplant phase. In particular, the unique nature of hepatic-leukocyte interactions appears to play a crucial role in the ability of the liver to silence the recipient alloimmune response. In this review, we will summarize the evidence regarding the potential mechanisms that mediate the critical early phase in the generation of hepatic allograft tolerance.
    MeSH term(s) Animals ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Graft Rejection/immunology ; Graft Rejection/metabolism ; Graft Rejection/prevention & control ; Graft Survival/drug effects ; Humans ; Immunosuppressive Agents/adverse effects ; Liver/drug effects ; Liver/immunology ; Liver/metabolism ; Liver/surgery ; Liver Transplantation/adverse effects ; Lymphocyte Activation ; Mice, Transgenic ; Time Factors ; Transplantation Tolerance/drug effects ; Treatment Outcome
    Chemical Substances Immunosuppressive Agents
    Language English
    Publishing date 2020-09-11
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.01908
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  5. Article ; Online: Adverse childhood experiences and sexual health outcomes and risk behaviors among a nationwide sample of men who have sex with men.

    Bertolino, Daniel F / Sanchez, Travis H / Zlotorzynska, Maria / Sullivan, Patrick S

    Child abuse & neglect

    2020  Volume 107, Page(s) 104627

    Abstract: Background: Adverse Childhood Experiences (ACEs) are associated with a wide range of increased risk behaviors and health consequences, they have not been extensively described in all subpopulations.: Objective: The specific objectives of the study ... ...

    Abstract Background: Adverse Childhood Experiences (ACEs) are associated with a wide range of increased risk behaviors and health consequences, they have not been extensively described in all subpopulations.
    Objective: The specific objectives of the study were to describe the prevalence of predefined ACEs among a nationwide sample of men who have sex with men (MSM) and determine associated HIV or sexually transmitted infection (STI) related health outcomes, testing practices, and risk behaviors.
    Participants and setting: Eligible participants were MSM aged 18 years or older who reported male-male sex in the past 12 months.
    Methods: Data were obtained from the 2015 cycle of the American Men's Internet Survey, these data were collected between September 2015 and April 2016, and contained questions related to 8 ACE exposure categories. During analyses conducted between September 2017 and April 2018, multiple log-binomial models were fit to assess associations.
    Results: Among 2590 participants, 79.7 % reported exposure to one or more ACE category. Participants exposed to any ACE were more likely to report STI testing (adjusted prevalence ratio [aPR]: 1.07; 95 % confidence interval [95 %-CI]: 1.00, 1.15), illicit substance use (aPR: 1.23, 95 %-CI: 1.05, 1.46), and condomless anal intercourse with another man (aPR: 1.13, 95 %-CI: 1.03, 1.21).
    Conclusions: There is a high overall ACE burden among MSM nationally, with potential influences on key HIV/STI behaviors in later life. ACE exposure should be routinely assessed, prevention is ideal but appropriate measures such as trauma informed care should also be considered for adult MSM accessing HIV and STI-related services.
    MeSH term(s) Adolescent ; Adult ; Adverse Childhood Experiences/psychology ; Adverse Childhood Experiences/trends ; Cross-Sectional Studies ; HIV Infections/epidemiology ; HIV Infections/prevention & control ; HIV Infections/psychology ; Homosexuality, Male/psychology ; Humans ; Male ; Middle Aged ; Outcome Assessment, Health Care/trends ; Risk-Taking ; Sexually Transmitted Diseases/epidemiology ; Sexually Transmitted Diseases/prevention & control ; Sexually Transmitted Diseases/psychology ; Unsafe Sex/prevention & control ; Unsafe Sex/psychology ; Young Adult
    Language English
    Publishing date 2020-07-16
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 799143-5
    ISSN 1873-7757 ; 0145-2134
    ISSN (online) 1873-7757
    ISSN 0145-2134
    DOI 10.1016/j.chiabu.2020.104627
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    Zs.A 1437: Show issues Location:
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  6. Article: Corrigendum: Malaria and the liver: immunological hide-and-seek or subversion of immunity from within?

    Bertolino, Patrick / Bowen, David G

    Frontiers in microbiology

    2015  Volume 6, Page(s) 460

    Abstract: This corrects the article on p. 41 in vol. 6, PMID: 25741320.]. ...

    Abstract [This corrects the article on p. 41 in vol. 6, PMID: 25741320.].
    Language English
    Publishing date 2015-05-13
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2015.00460
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  7. Article: Impaired function of dendritic cells translocating the liver sinusoids: a veto effect contributing to intrahepatic tolerance?

    Bertolino, Patrick

    European journal of immunology

    2008  Volume 38, Issue 4, Page(s) 938–941

    Abstract: Due to its unique architecture and conditions of blood flow, the liver is acknowledged as an immunologically unusual organ associated with primary activation of naïve T cells and the induction of tolerance. Several mechanisms have been proposed to be ... ...

    Abstract Due to its unique architecture and conditions of blood flow, the liver is acknowledged as an immunologically unusual organ associated with primary activation of naïve T cells and the induction of tolerance. Several mechanisms have been proposed to be involved in this process. Most suggest that naïve T cells activated in situ in the hepatic sinusoids are deleted or silenced following activation by liver cells acting as antigen presenting cells. Hepatocytes, liver sinusoidal endothelial cells and bone marrow-derived cells (including Kupffer cells and DC) have been shown to support primary activation in situ and play some role in tolerance induction. Although most liver DC have been described to be immature and located in sites inaccessible to naïve T cells, some blood-borne DC have been shown to translocate via the sinusoids where naïve T cells recirculate. Thus, the presence of mature DC with potential immunogenicity in the sinusoids might give contradictory signals to the naïve T cells activated within this organ. In this issue of the European Journal of Immunology, liver sinusoidal endothelial cells are shown to impair the DC ability to induce the proliferation of naïve T cells in vitro via an unknown mechanism. Although these findings need to be confirmed in a physiological setting, regulation of the function of DC translocating the sinusoids might represent a new mechanism contributing to T cell tolerance in the liver.
    MeSH term(s) Animals ; Cell Movement/immunology ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Humans ; Immune Tolerance/immunology ; Liver/blood supply ; Liver/immunology ; Lymphocyte Activation/immunology
    Language English
    Publishing date 2008-04
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.200838296
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    Zs.A 489: Show issues Location:
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  8. Article: Malaria and the liver: immunological hide-and-seek or subversion of immunity from within?

    Bertolino, Patrick / Bowen, David G

    Frontiers in microbiology

    2015  Volume 6, Page(s) 41

    Abstract: During the pre-erythrocytic asymptomatic phase of malarial infection, sporozoites develop transiently inside less than 100 hepatocytes that subsequently release thousands of merozoites. Killing of these hepatocytes by cytotoxic T cells (CTLs) confers ... ...

    Abstract During the pre-erythrocytic asymptomatic phase of malarial infection, sporozoites develop transiently inside less than 100 hepatocytes that subsequently release thousands of merozoites. Killing of these hepatocytes by cytotoxic T cells (CTLs) confers protection to subsequent malarial infection, suggesting that this bottleneck phase in the parasite life cycle can be targeted by vaccination. During natural transmission, although some CTLs are generated in the skin draining lymph nodes, they are unable to eliminate the parasite, suggesting that the liver is important for the sporozoite to escape immune surveillance. The contribution of the organ to this process is unclear. Based on the known ability of several hepatic antigen-presenting cells (APCs) to induce primary activation of CD8 T cells and tolerance, malarial antigens presented by both infected hepatocytes and/or hepatic cross-presenting APCs should result in tolerance. However, our latest model predicts that due to the low frequency of infected hepatocytes, some T cells recognizing sporozoite epitopes with high affinity should differentiate into CTLs. In this review, we discuss two possible models to explain why CTLs generated in the liver and skin draining lymph nodes are unable to eliminate the parasite: (1) sporozoites harness the tolerogenic property of the liver; (2) CTLs are not tolerized but fail to detect infected cells due to sparse infection of hepatocytes and the very short liver stage. We propose that while malaria sporozoites might use the ability of the liver to tolerize both naive and effector cells, they have also developed strategies to decrease the probability of encounter between CTLs and infected liver cells. Thus, we predict that to achieve protection, vaccination strategies should aim to boost intrahepatic activation and/or increase the chance of encounter between sporozoite-specific CTLs and infected hepatocytes.
    Language English
    Publishing date 2015-02-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2015.00041
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  9. Article: Nanoemulsions of synthetic rhamnolipids act as plant resistance inducers without damaging plant tissues or affecting soil microbiota.

    Mottola, Milagro / Bertolino, María C / Kourdova, Lucille Tihomirova / Valdivia Pérez, Jessica Aye / Bogino, María Florencia / Nocelli, Natalia E / Chaveriat, Ludovic / Martin, Patrick / Vico, Raquel V / Fabro, Georgina / Fanani, María Laura

    Frontiers in plant science

    2023  Volume 14, Page(s) 1195718

    Abstract: Plant pathogens and pests can cause significant losses in crop yields, affecting food security and the global economy. Many traditional chemical pesticides are used to combat these organisms. This can lead to the development of pesticide-resistant ... ...

    Abstract Plant pathogens and pests can cause significant losses in crop yields, affecting food security and the global economy. Many traditional chemical pesticides are used to combat these organisms. This can lead to the development of pesticide-resistant strains of pathogens/insects and negatively impact the environment. The development of new bioprotectants, which are less harmful to the environment and less likely to lead to pesticide-resistance, appears as a sustainable strategy to increase plant immunity. Natural Rhamnolipids (RL-Nat) are a class of biosurfactants with bioprotectant properties that are produced by an opportunistic human pathogen bacterium. RL-Nat can act as plant resistance inducers against a wide variety of pathogens. Recently, a series of bioinspired synthetic mono-RLs produced by green chemistry were also reported as phytoprotectants. Here, we explored their capacity to generate novel colloidal systems that might be used to encapsulate bioactive hydrophobic compounds to enhance their performance as plant bioprotectants. The synthetic mono-RLs showed good surfactant properties and emulsification power providing stable nanoemulsions capable of acting as bio-carriers with good wettability. Synthetic RLs-stabilized nanoemulsions were more effective than RLs suspensions at inducing plant immunity, without causing deleterious effects. These nanoemulsions were innocuous to native substrate microbiota and beneficial soil-borne microbes, making them promising safe bio-carriers for crop protection.
    Language English
    Publishing date 2023-08-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2613694-6
    ISSN 1664-462X
    ISSN 1664-462X
    DOI 10.3389/fpls.2023.1195718
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  10. Article ; Online: The liver contains distinct interconnected networks of CX3CR1

    English, Kieran / Tan, Sioh Yang / Kwan, Rain / Holz, Lauren E / Sierro, Frederic / McGuffog, Claire / Kaisho, Tsuneyasu / Heath, William R / MacDonald, Kelli Pa / McCaughan, Geoffrey W / Bowen, David G / Bertolino, Patrick

    Immunology and cell biology

    2022  Volume 100, Issue 6, Page(s) 394–408

    Abstract: Portal tracts are key intrahepatic structures where leukocytes accumulate during immune responses. They contain the blood inflow, which includes portal blood from the gut, and lymphatic and biliary outflow of the liver, and as such represent a key ... ...

    Abstract Portal tracts are key intrahepatic structures where leukocytes accumulate during immune responses. They contain the blood inflow, which includes portal blood from the gut, and lymphatic and biliary outflow of the liver, and as such represent a key interface for potential pathogen entry to the liver. Myeloid cells residing in the interstitium of the portal tract might play an important role in the surveillance or prevention of pathogen dissemination; however, the exact composition and localization of this population has not been explored fully. Our in-depth characterization of portal tract myeloid cells revealed that in addition to T lymphocytes, portal tracts contain a heterogeneous population of MHCII
    MeSH term(s) Dendritic Cells ; Liver ; Macrophages
    Language English
    Publishing date 2022-06-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1111/imcb.12559
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