Control of Innate and Adaptive Immune Responses during Infectious Diseases Julio Aliberti Editor Control of Innate and Adaptive Immune Responses during Infectious Diseases Editor Julio Aliberti Associate Professor Divisions of Molecular Immunology and Pulmonary Medicine Cincinnati Children’s Hospital Medical Center and School of Medicine University of Cincinnati Cincinnati, OH, USA julio.aliberti@cchmc.org ISBN 978-1-4614-0483-5 e-ISBN 978-1-4614-0484-2 DOI 10.1007/978-1-4614-0484-2 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2011936972 © Springer Science+Business Media, LLC 2012 All rights reserved This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Preface Upon infection, pathogen and host perform a complex interaction that ultimately aims to achieve elimination of the invading microbe with the least amount of damage to host tissues and organs Interestingly, both sides of this equation co-evolved several mechanisms that mediate pathogen recognition, initiation and expansion of immune responses, neutralization of toxic elements and elimination of replicating organisms and finally healing and remodeling of damaged tissues On one side pathogens evolved mechanisms to evade recognition and killing, while on the other side, host express numerous (sometimes redundant) mechanisms of recognition and elimination of the pathogen Nonetheless, it is clear that an absolute successful strategy on the pathogen side would be lethal to both host and pathogen Therefore, several evasion mechanisms are seen among several microbes The most successful ones are not necessarily the most abundantly found within the host, but those that can achieve transmission On the other hand, hosts need a robust and extended immune response in order to expand memory cells This critical balance is where the co-evolution between host and pathogens lies This book covers several aspects of induction, control and evasion of host immune response during infectious diseases Multiple aspects are covered and each chapter focuses on one prominent infectious agent Cincinnati, OH Julio Aliberti v Contents Resolution of Inflammation During Toxoplasma gondii Infection Julio Aliberti Mechanisms of Host Protection and Pathogen Evasion of Immune Response During Tuberculosis Andre Bafica and Julio Aliberti NKT Cell Activation During (Microbial) Infection Jochen Mattner Regulation of Innate Immunity During Trypanosoma cruzi Infection Fredy Roberto Salazar Gutierrez B Cell-Mediated Regulation of Immunity During Leishmania Infection Katherine N Gibson-Corley, Christine A Petersen, and Douglas E Jones 23 39 69 85 Control of the Host Response to Histoplasma Capsulatum George S Deepe, Jr 99 Modulation of T-Cell Mediated Immunity by Cytomegalovirus 121 Chris A Benedict, Ramon Arens, Andrea Loewendorf, and Edith M Janssen T Cell Responses During Human Immunodeficiency Virus (HIV)-1 Infection 141 Claire A Chougnet and Barbara L Shacklett Index 171 vii Contributors Julio Aliberti, Ph.D Associate Professor, Divisions of Molecular Immunology and Pulmonary Medicine, Cincinnati Children’s Hospital Medical Center and School of Medicine, University of Cincinnati, Cincinnati, OH, USA julio.aliberti@cchmc.org Ramon Arens Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA Andre Bafica, M.D., Ph.D Assistant Professor, Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina, Florianopolis, SC, Brazil andre.bafica@ufsc.br Chris A Benedict Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA benedict@liai.org Claire A Chougnet Division of Molecular Immunology, Cincinnati Children’s Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA Claire.Chougnet@cchmc.org George S Deepe Jr, M.D Professor, Veterans Affairs Hospital, Cincinnati, OH, USA; Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA george.deepe@uc.edu Katherine N Gibson-Corley Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA, USA Fredy Roberto Salazar Gutierrez, 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description, 50–51 microbial infections, dual recognition, 51 Salmonella and TCR signaling, 51 direct recognition, microbial GSLs Agelas mauritianus, 52–53 alphaglucuronylceramides, 52 description, 52 lyme disease, 53 Sphingomonas/Novosphingobium, 52 gram-negative bacteria, 50 parasitic, helminth and fungal infections Candida albicans and Aspergillus fumigatus, 54 control parasitic replication, 54 Plasmodium, 54 role and anti-parasite responses, 54 viral infections detection, viral pathogens, 53 Hepatitis B virus (HBV) model, 53–54 immune defense strategy, 54 iNKT role, 53 lethal outcome, Epstein-Barr virus, 53 role and SAP-Fyn signaling, 53 Bafica, A., 23–34 B and T lymphocyte attenuator (BTLA), 133 B cell-mediated regulation, Leishmania antibodies, 86 arm, immune system, 85–86 CMI, 85 humoral immunity, 86 IL–1 and IL–6, 88 intercellular pathogen clinical infection, 90–91 description, 89 murine models, 92–93 Th1 vs Th2, 89–90 intracellular pathogen antibodies role, 86–87 CMI effects, 86 immune control, Ehrlichia chaffeensis, 87 proinflammator vs anti-inflammatory, 87–88 Th1 response, Fc R, 86 macropages activation and antibodies J Aliberti (ed.), Control of Innate and Adaptive Immune Responses during Infectious Diseases, DOI 10.1007/978-1-4614-0484-2, © Springer Science+Business Media, LLC 2012 171 172 B cell-mediated regulation, Leishmania (cont.) functions, 88–89 NADPH oxidase, 89 nitric oxide (NO) production, 88 superoxide production, 89 Benedict, C.A., 121 BTLA See B and T lymphocyte attenuator Buzoni-Gatel, D., 11 C CD1 system and NKT cells description, 41 group II (CD1d) description, 42 in mouse, 42 restricted diverse type II iNKT cells, 43–44 restricted type I iNKT cells, 42–43 group III (CD1e), 44 group I (CD1a, b, c), mycobacterium tuberculosis, 41 mediated presentation, GSLs, 49 MHC gene complex, 41 self-GSL antigens endogenous presentation, 49 -hexosaminidase B, 50 isoglobotrihexosylceramide (iGb3), 49–50 regulation, 50 self-lipid antigens, 50 species distribution birds, 44 existence, 44 human and guinea pigs, 44–45 isoforms, 44 mycobacteria-infection, 45 CD4+ T cells and HIV affecting subsets regulatory T cells, 149–150 Th17 cells, 149 Th1/Th2 cells, 148–149 AIDS and depletion disease cell loss, morbidity and mortality, 145 cross-linking, 146–147 cytopathic effects, virus, 145–146 GI loss, 145 IFNs effects, 147 increases “bystander” cells, 146 “natural” vs “non-natural” hosts, 145 primary target cells, 146 immune dysregulation abnormalities, 147 Index chronic “tickling”, 148 defects, 147heterodimeric integrin 7, 148 in vitro CD4+ T cells, 147 CD8+ T cells responses, HIV acute/early infection, 154 function and dysfunction, chronic infection ageing, immune system, 155 characterization, 154 contribution, 155 immune exhaustion and LCMV, 154 immune control, 151 lessons and HIV controllers antiretroviral therapy, 152 GWAS, 152 HLA-B*35 alleles and AIDS, 153 human HLA-B*5701, Mamu-B*17, 153 in silico model, 153 MHC class I and II alleles, 152 natural killer (NK) cell function, 152–153 Cell mediated immunity (CMI), 85–87 Chemokine receptors CCR2 binds CCL2, 111, 113 inability, CCL2 and CCL7, 112 L-arginine, fungal elimination, 111, 112 CCR5 IL–17A neutralization, 113 role, T and Th17 cells, 113, 114 Chougnet, C.A., 141 CMI See Cell mediated immunity (CMI) CMV See Cytomegalovirus Culture-derived tachyzoites (STag), 4, 13 Cytomegalovirus (CMV) adaptive T cell responses costimulation, 127–128 MHC-TCR interactions, 126–127 apoptosis pathways, 134 CD8+ and CD4+ T cells HCMV, 125 immunomodulatory effects, DCs, 126 MCMV replication, 124–125 memory inflation, 125–126 DCs, 122–124 epidemiology and pathology HCMV infection, 122 risk factor, 122 herpesviruses, 121 immunosuppressive machinations, 134 modification, T cells B7 costimulation, 130–131 cytokines, 133–134 HVEM/BTLA interactions, 133 Index MHC expressions, 128–130 PD–1/PDL–1 pathway, 132–133 soluble positive cosignals, 131–132 NK and NKT cells, 124 D Debbabi, H., 11 Deepe, G.S Jr., 99 Dendritic cells (DCs) CMV cytokines, 122–123, 131–132 HCMV infection, 126 immune modulatory gene products, 123–124 MCMV, 128, 132 MHC molecules, 126 negative net signal, 128, 129 NK cells, 124 PD-L1, 132 positive net signal, 128, 129 cross-presentation pathway, DC, 104 cytomegalovirus (CMV), 122–124 Histoplasma capsulatum bind and ingest, 103, 104 cross-presentation pathway, 104 population, 101 yeast cells, 103, 104 immunomodulatory effects, 126 intracellular lifestyle, 104 microbial recognition, neutrophils, 104 paralysis, 13 production, DC, 131–132 G Gibson-Corley, K.N., 85–93 Glycosphingolipid (GSL) bacterial and non-bacterial infection Agelas mauritianus, 52–53 alphaglucuronylceramides, 52 description, 52 lyme disease, 53 Sphingomonas/Novosphingobium, 52 CD1 system and NKT cells endogenous presentation, 49 -hexosaminidase B, 50 isoglobotrihexosylceramide (iGb3), 49–50 mediated presentation, GSLs, 49 regulation, 50 self-lipids reportoire, 50 iNKT cell activation GSL antigens and structures, 40 173 in humans, 56 self-GSL antigens, 49–50 Gram-negative, LPS-positive bacteria, 50–53 Granuloma formation and bacilli tuberculosis chronic maintenance, 28 description, 27–28 fibrous capsule, 28 IFN- , 29 IL–10, 30 lipoxins, 29–30 TGF- , 30 TNF, 28–29 Gutoerrez, F.R.S., 69–81 H HAART See Highly Active Anti-Retroviral Therapy (HAART) HCMV See Human cytomegalovirus Hepatitis B virus (HBV) model, 53–54 Herpesvirus entry mediator (HVEM), 133 Highly Active Anti-Retroviral Therapy (HAART), 143, 155–156 Histoplasma capsulatum characterization, inflammatory response M , 101 neutrophils, 100–101 T and B cells, 101 chemokines and chemokine receptors CCR2, 111–113 CCR5, 113 cytokines GM-CSF, 108 IL–1, 108 IL–4, 110 IL–10, 111 IL–17 and Th17, 109 IL–12/IFN- axis, 107–108 TNF- , 109–110 description, 99–100 granuloma intracellular pathogens, 101 T cells, 102 intracellular lifestyle DC, 104 M , 102–103 neutrophils, 103–104 leukotrienes, 113–114 lymphoid cell, infection control B cells, 107 T cells, 104–107 TCR, 105–106 174 Human cytomegalovirus (HCMV) CD4 and CD8 T cells, 125 glycoprotein products, 129 IL–10, 133–134 NK cells, 124 Human immunodeficiency virus (HIV)–1 anti-retroviral therapy effect HAART, 155–156 search immune based therapies, 157–158 CD4+ T cells depletion disease, 145–147 immune dysregulation, 147–148 regulatory T cells, 149–150 Th17 cells, 149 Th1/Th2 cells, 148–149 CD8+ T-cells function and dysfunction, chronic infection, 154–155 immune control, 151 lessons and controllers, 152–153 responses, acute/early infection, 154 cell-cell interaction, 158 discovery, 158 experimental models limitation, heterologous viruses, 144 rodents, 143 SIV and Rhesus macaques (RM), 143–144 immune system, humans and honhumans, 158 life cycle CD4 T cells, 142 gag, pol and env genes, 142 HAART, 143 mRNA encoding, 143 replication, 143 Tat and Rev, transport RNAs, 142–143 T cell activation, 158 transmission cis-/trans-infection, 144 clade B virus, 144 draining lumph nodes, 144 mucosal exposure, 144 phenotypic analysis, 144 route and mucosal infections, 145 virus dose and human transmission, 144–145 HVEM See Herpesvirus entry mediator I IL See Interleukin Immunopathology mechanism, Toxoplasma gondii Index IL–27 and suppression, 12–13 IL–22 role, 11–12 inflammation redundancy and control, 14–15 interleukin–10 central role, 11 mediators and antigen processing, modulatory activities, 10 neutralization, 10 pathogens and poxviruses, 9–10 pro-inflammatory responses, 10 TGF and IL–35, lipoxin A4 control, 14 “DC paralysis”, 13 injection, STAg, 13 Mycobacterium tuberculosis, 16–17 pathogen evasion, 15–16 production, 14 receptors and evidence role, 13 resolution phase cardinal signs, controlling and promoting, homeostasis, omega–3 PUFA/fish oils, 8–9 tissue injury, cause and consequences, TGFdescription, 10 macrophage deactivator, 11 mucosal host/pathogen interaction, 11 role, 12 iNKT cells, humans CD1d-restricted, 55 infections, Novosphingobium/ Sphingomonas spp osocomial and septic shock, 56 xenobiotic-metabolizing properties, 55–56 PBC association GSL recognition role, 56 pathogenesis, 56–57 PDC-E2 homologues, 57 primary biliary cirrhosis (PBC), 55 V 24 iNKT cells, 55 Innate immunity regulation, Trypanosoma cruzi cardiomyopathy, 70–71 cell migration, 79 Chagas’ disease, 69 characterization, 70 cytokines, 78 description, 69 development, cardiac damages, 71 diagnosis, 70 Index GIPL and Tc52 activation, 73 intracellular parasite, 73 production, TGF- and IL–10 and IL.12p70, 73 TLR2 activation, 72 TLR2-/-and MyD88-/-mice, 73 GIPL recognition, 73–74 glycoinositolphospholipids (GIPL), 71 in human beings, 70 interaction and evolution, 71 life cycle, 70 mechanisms, innate immune system, 72 MMP, 80 nitric oxide (NO) APC and T cells and induce apoptosis, 75 deficiency impact, 76 donors and control, 75 production and role, 75 response mechanisms, 75 versatile immune mediators, 75 NLR participation, 74–75 phagocytic cells intracellular replication, 78 intracellular signaling, 77–78 macrophages activation, 76 mechanisms, 78 parasite killing, 77 TLR, 71 TLR9 involvement, 74 Interleukin (IL) cmvIL–10, 133–134 HCMV, IL–10, 133–134 Histoplasma capsulatum IL–1, 108 IL–4, 110 IL–10, 111 IL–17 and Th17, 109 IL–12/IFN- axis, 107–108 IL–1 receptor, 108 IL–17A neutralization, 113 IL–12 induction, inflammation resolution (see Toxoplasma gondii infection) immune based therapies, IL–2 effects, 157 Leishmania, IL and 6, 88 prevent immunopathology mechanism IL–22, 11–12 IL–27, 12–13 Toxoplasma gondii IL–10, IL–27 and suppression, 12–13 IL–12 induction (see Toxoplasma gondii and inflammation resolution) IL–22 role, 11–12 175 Trypanosoma cruzi IL–10, 73 IL.12p70, 73 tuberculosis, IL–10, 30 Invariant Natural Killer T (iNKT) cell activation, microbial infection bacterial infection bystander indirect activation, 50–51 cognate recognition, GSL antigens, 52–53 CD1 presentation, 49 CD1 system division, 41 formation, 41 group I (CD1a, b, c), 41 group II (CD1d), 42–44 group III, (CD1e), 44 species distribution, 44–45 function antibody production, 48 anti-microbial activity, 48 autoreactivity, 46 bacteria and virus detection, 45 circuits and molecular mechanisms, 46 deficient CD1d0/J 180 mice, 45 interactions, 47–48 mechanisms, 48 natural and immune rejection, 45 systemic administration, 46–47 Th1 or Th2 cytokines, 45 trans-activation, 47 type I diabetes, 45–46 GSL antigens and structures, 40 in human correlation, 55 Novovosphingobium/Sphingomonas spp., 55–56 primary biliary cirrhosis, 56–57 MHC class I, 40 mouse model infection, 57–58 non-bacterial infection parasitic, helminth and fungal infections, 54 viral infections, 53–54 role, 40 self-GSL antigens, 49–50 TCR, cell population, 40 V124 TCR, human, 40 V114 TCR, mice, 40 J Janssen, E.M., 121 Jones, D.E., 85–93 176 K Koch, R., 23 L Lipoxins M tuberculosis in humans, ALOX5, 29–30 5-LO-dependent, 29 risk, 30 role, 29 Toxoplasma gondii control, 14 “DC paralysis”, 13 injection, STAg, 13 mycobacterium tuberculosis, 16–17 vs Mycobacterium tuberculosis, 17 pathogen evasion, 15–16 production, 14 receptors and evidence role, 13 Loewendorf, A., 121 M Macrophages (M ), Histoplasma capsulatum CD11/CD18 adhesin receptors, 102, 103 CD8+ cytotoxic T cells, 106 cross-presentation pathway, DC, 104 granuloma, 101 growth inhibition, 103 IL–4, 110 neutrophils, 103 yeast cells, 102, 103 Major histocompatibility complex (MHC) CD1 system and NKT cells, 41 CD8+ T cells responses, HIV, 152 class I expression antigen-presentation, 128–129 glycoprotein products, 129 “immunoevasion” genes, 129–130 class II expression antigen presentation, 130 proteolytic degradation process, 130 CmvIL–10, 133–134 cytomegalovirus (CMV), 126–130 dendritic cells, 126 iNKT cell activation, 40 MCMV, 128–129 TCR interactions cross-presentation, 127 exogenous and endogenous pathway, 126–127 Matrix Metalloproteinases (MMP), 80 Index Mattner, J., 31–58 MCMV See Murine cytomegalovirus MHC See Major histocompatibility complex Mixed lymphocyte reactions (MLR), 128 M See Macrophages MLR See Mixed lymphocyte reactions Mouse model infection, 57–58 Murine cytomegalovirus (MCMV) CD8 and CD4 T cells, 124–125 m138 gene, 131 MHC class I pathway, 128–129 m157 protein, 124 N NADPH oxidase, 87, 89 Natural killer (NK) cells absence, 27 accumulation, 27 CMV DCs, 124 MCMV m157 protein, 124 depletion, 27 role, 26 Natural vs non-natural hosts, 145 Neutorphils Histoplasma capsulatum DC, 104 human defensins, 103–104 IL–4, 110 yeast cells, M , 103 tuberculosis acute pulmonary tuberculosis, 24 definition, 24 depletion, 24 mouse strains, 25 potential role, 25 protection, 24–25 Nitric oxide (NO) Leishmania, 88 Trypanosoma cruzi deficiency impact, 76 donors and control, 75 production and role, 75 response mechanisms, 75 versatile immune mediators, 75 NK cells See Natural killer cells P PDL–1 See Programmed death ligand Petersen, C.A., 85–93 Programmed death ligand (PDL–1), 132–133 Proinflammator vs anti-inflammatory, 87–88 Index S Shacklett, B.L., 141 Superoxide production, 89 T T cell receptor (TCR) cell population V124 TCR, human, 40 V114 TCR, mice, 40 Histoplasma capsulatum CD3+, 105 protective immunity, 105–106 pulmonary infection, 105 reactivation histoplasmosis, 106 interactions cross-presentation, 127 exogenous and endogenous pathway, 126–127 lymphoid cell, infection control, 105–106 T cells B7 costimulation CD28 and CTLA–4, 130–131 MCMV m138 gene, 131 positive cosignaling pathways, 131 costimulation B7 family, 127 positive and negative net signals, 128, 129 TNF receptor and soluble mediators, 127 cytokines cmvIL–10 and IDO, 133–134 HCMV, 134 production, DC, 131–132 Histoplasma capsulatum CCR5, 113, 114 CD4+ and CD8+ cells, 104–105 granuloma, 102 IL–1 receptor, 108 PD ligands, 106 promote immunity, 106 receptors, CD3+, 105 regulatory, 107 TNF- production, 105, 109 HVEM/BTLA interactions, 133 MHC expressions, 128–130 MHC-TCR interactions cross-presentation, 127 exogenous and endogenous pathway, 126–127 MLR, 128 PD–1/PDL–1 pathway B7-CD28 pathway, 132–133 177 cell cycle arrest, 132 negative cosignaling, 132 TCR See T cell receptor Th1 vs Th2, 89–90 TNF- See Tumor necrosis factor-alpha Toll-like receptors (TLRs) microbial recognition, 5–6 signaling, 51 Trypanosoma cruzi TLR, 71 TLR2 activation, 72 TLR2-/-and MyD88-/-mice, 73 TLR9 involvement, 74 Toxoplasma gondii and inflammation resolution cysts and bradyzoites, description, felines, cat, in human, IFN- , Th1 cells and microbicidal activity activation factors and parasite strains, components, immune responses mechanisms, investigation, 18 life cycle, microbial recognition and IL–12 induction biochemical signaling, CCR5 role, complexity and protection, cyclophillin–18, cytoplasmic protein profillin, hypothesis, dendritic cells, IFN- , immune response and pathogen, IRF–8, mice, macrophages, neutrophils and DCs, p38 MAP kinases, 6–7 TLRs, 5–6 transcription factors, use STAg, 4–5 natural conditions infection, parasite replication, prevent immunopathology mechanism endogenous LXA4, 15–17 IL–22, 11–12 IL–27, 12–13 inflammation redundancy and control, 14–15 interleukin–10, 9–10 lipoxin A4, 13–14 resolution phase, 8–9 TGF-B, 10–11 protozoan apicomplexa parasite, survival, oocysts, 2, 178 Toxoplasma gondii and inflammation resolution (cont.) symptoms development and risk, tachyzoites replication and “dripping” effect, transmission, Toxoplasma gondii vs Mycobacterium tuberculosis, 17 Tuberculosis, host protection and pathogen evasion BCG and treatment, 24 BCG vaccine, 33–34 disease reactivation AIDS and TNF, 32 drug and treatment, 32 effects, 33 epidemiology, 32 HIV, 32–33 granuloma formation and bacilli (see Granuloma formation and bacilli) history, 23 immune response cell wall components, 31 host cell signalling, 32 mycobacterial dormancy, 31–32 phagosome-lysosome fusion, 31 Index infection and innate immunity dendritic cells, 26 natural killer cells, 26–27 neutorphils, 24–25 regulatory T cells, 27 T cells, 25–26 risk, 24 WHO, 23–24 Tumor necrosis factor-alpha (TNF- ), Histoplasma capsulatum primary and secondary infection, 109 T cells, 106 TNF receptors, 109–110 V Vaccines BCG, 33 HIV, 33 Viral infections detection, viral pathogens, 53 Hepatitis B virus (HBV) model, 53–54 immune defense strategy, 54 iNKT role, 53 lethal outcome, Epstein-Barr virus, 53 role and SAP-Fyn signaling, 53 .. .Control of Innate and Adaptive Immune Responses during Infectious Diseases Julio Aliberti Editor Control of Innate and Adaptive Immune Responses during Infectious Diseases Editor... Immunology and Parasitology, Federal University of Santa Catarina, Florianopolis, SC, Brazil e-mail: andre.bafica@ufsc.br J Aliberti (ed.), Control of Innate and Adaptive Immune Responses during Infectious. .. Aliberti (ed.), Control of Innate and Adaptive Immune Responses during Infectious Diseases, DOI 10.1007/978-1-4614-0484-2_1, © Springer Science+Business Media, LLC 2012 J Aliberti Ingestion of oocysts