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Increased Monocyte Turnover from Bone Marrow Correlates with Severity of SIV Encephalitis and CD163 Levels in Plasma


Cells of the myeloid lineage are significant targets for human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in monkeys. Monocytes play critical roles in innate and adaptive immunity during inflammation. We hypothesize that specific subsets of monocytes expand with AIDS and drive central nervous system (CNS) disease. Additionally, there may be expansion of cells from the bone marrow through blood with subsequent macrophage accumulation in tissues driving pathogenesis. To identify monocytes that recently emigrated from bone marrow, we used 5-bromo-2′-deoxyuridine (BrdU) labeling in a longitudinal study of SIV-infected CD8+ T lymphocyte depleted macaques. Monocyte expansion and kinetics in blood was assessed and newly migrated monocyte/macrophages were identified within the CNS. Five animals developed rapid AIDS with differing severity of SIVE. The percentages of BrdU+ monocytes in these animals increased dramatically, early after infection, peaking at necropsy where the percentage of BrdU+ monocytes correlated with the severity of SIVE. Early analysis revealed changes in the percentages of BrdU+ monocytes between slow and rapid progressors as early as 8 days and consistently by 27 days post infection. Soluble CD163 (sCD163) in plasma correlated with the percentage of BrdU+ monocytes in blood, demonstrating a relationship between monocyte activation and expansion with disease. BrdU+ monocytes/macrophages were found within perivascular spaces and SIVE lesions. The majority (80–90%) of the BrdU+ cells were Mac387+ that were not productively infected. There was a minor population of CD68+BrdU+ cells (<10%), very few of which were infected (<1% of total BrdU+ cells). Our results suggest that an increased rate of monocyte recruitment from bone marrow into the blood correlates with rapid progression to AIDS, and the magnitude of BrdU+ monocytes correlates with the severity of SIVE.


Vyšlo v časopise: Increased Monocyte Turnover from Bone Marrow Correlates with Severity of SIV Encephalitis and CD163 Levels in Plasma. PLoS Pathog 6(4): e32767. doi:10.1371/journal.ppat.1000842
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000842

Souhrn

Cells of the myeloid lineage are significant targets for human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in monkeys. Monocytes play critical roles in innate and adaptive immunity during inflammation. We hypothesize that specific subsets of monocytes expand with AIDS and drive central nervous system (CNS) disease. Additionally, there may be expansion of cells from the bone marrow through blood with subsequent macrophage accumulation in tissues driving pathogenesis. To identify monocytes that recently emigrated from bone marrow, we used 5-bromo-2′-deoxyuridine (BrdU) labeling in a longitudinal study of SIV-infected CD8+ T lymphocyte depleted macaques. Monocyte expansion and kinetics in blood was assessed and newly migrated monocyte/macrophages were identified within the CNS. Five animals developed rapid AIDS with differing severity of SIVE. The percentages of BrdU+ monocytes in these animals increased dramatically, early after infection, peaking at necropsy where the percentage of BrdU+ monocytes correlated with the severity of SIVE. Early analysis revealed changes in the percentages of BrdU+ monocytes between slow and rapid progressors as early as 8 days and consistently by 27 days post infection. Soluble CD163 (sCD163) in plasma correlated with the percentage of BrdU+ monocytes in blood, demonstrating a relationship between monocyte activation and expansion with disease. BrdU+ monocytes/macrophages were found within perivascular spaces and SIVE lesions. The majority (80–90%) of the BrdU+ cells were Mac387+ that were not productively infected. There was a minor population of CD68+BrdU+ cells (<10%), very few of which were infected (<1% of total BrdU+ cells). Our results suggest that an increased rate of monocyte recruitment from bone marrow into the blood correlates with rapid progression to AIDS, and the magnitude of BrdU+ monocytes correlates with the severity of SIVE.


Zdroje

1. SoulasC

DonahueRE

DunbarCE

PersonsDA

AlvarezX

2009 Genetically modified CD34+ hematopoietic stem cells contribute to turnover of brain perivascular macrophages in long-term repopulated primates. Am J Pathol 174 1808 1817

2. Gonzalez-MejiaME

DoseffAI

2009 Regulation of monocytes and macrophages cell fate. Front Biosci 14 2413 2431

3. van FurthR

1989 Origin and turnover of monocytes and macrophages. Curr Top Pathol 79 125 150

4. TushinskiRJ

OliverIT

GuilbertLJ

TynanPW

WarnerJR

1982 Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. Cell 28 71 81

5. LandsmanL

VarolC

JungS

2007 Distinct differentiation potential of blood monocyte subsets in the lung. J Immunol 178 2000 2007

6. WhitelawDM

1972 Observations on human monocyte kinetics after pulse labeling. Cell Tissue Kinet 5 311 317

7. VarolC

YonaS

JungS

2009 Origins and tissue-context-dependent fates of blood monocytes. Immunol Cell Biol 87 30 38

8. SawyerRT

StrausbauchPH

VolkmanA

1982 Resident macrophage proliferation in mice depleted of blood monocytes by strontium-89. Lab Invest 46 165 170

9. TarlingJD

LinHS

HsuS

1987 Self-renewal of pulmonary alveolar macrophages: evidence from radiation chimera studies. J Leukoc Biol 42 443 446

10. WijffelsJF

de RoverZ

BeelenRH

KraalG

van RooijenN

1994 Macrophage subpopulations in the mouse spleen renewed by local proliferation. Immunobiology 191 52 64

11. SwirskiFK

NahrendorfM

EtzrodtM

WildgruberM

Cortez-RetamozoV

2009 Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325 612 616

12. van FurthR

Diesselhoff-den DulkMM

1984 Dual origin of mouse spleen macrophages. J Exp Med 160 1273 1283

13. NahrendorfM

SwirskiFK

AikawaE

StangenbergL

WurdingerT

2007 The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 204 3037 3047

14. ArnoldL

HenryA

PoronF

Baba-AmerY

van RooijenN

2007 Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J Exp Med 204 1057 1069

15. Van FurthR

Diesselhoff-den DulkMC

MattieH

1973 Quantitative study on the production and kinetics of mononuclear phagocytes during an acute inflammatory reaction. J Exp Med 138 1314 1330

16. VolkmanA

CollinsFM

1974 The cytokinetics of monocytosis in acute salmonella infection in the rat. J Exp Med 139 264 277

17. OhgamiM

DoerschukCM

GieRP

EnglishD

HoggJC

1991 Monocyte kinetics in rabbits. J Appl Physiol 70 152 157

18. MeuretG

BammertJ

HoffmannG

1974 Kinetics of human monocytopoiesis. Blood 44 801 816

19. GotoY

HoggJC

SuwaT

QuinlanKB

van EedenSF

2003 A novel method to quantify the turnover and release of monocytes from the bone marrow using the thymidine analog 5′-bromo-2′-deoxyuridine. Am J Physiol Cell Physiol 285 C253 259

20. HasegawaA

LiuH

LingB

BordaJT

AlvarezX

2009 The level of monocyte turnover predicts disease progression in the macaque model of AIDS. Blood 114 2917 2925

21. BrownKN

WijewardanaV

LiuX

Barratt-BoyesSM

2009 Rapid influx and death of plasmacytoid dendritic cells in lymph nodes mediate depletion in acute simian immunodeficiency virus infection. PLoS Pathog 5 e1000413 doi:10.1371/journal.ppat.1000413

22. ShihCH

van EedenSF

GotoY

HoggJC

2005 CCL23/myeloid progenitor inhibitory factor-1 inhibits production and release of polymorphonuclear leukocytes and monocytes from the bone marrow. Exp Hematol 33 1101 1108

23. GotoY

HoggJC

WhalenB

ShihCH

IshiiH

2004 Monocyte recruitment into the lungs in pneumococcal pneumonia. Am J Respir Cell Mol Biol 30 620 626

24. WangX

DasA

LacknerAA

VeazeyRS

PaharB

2008 Intestinal double-positive CD4+CD8+ T cells of neonatal rhesus macaques are proliferating, activated memory cells and primary targets for SIVMAC251 infection. Blood 112 4981 4990

25. Fischer-SmithT

CroulS

SverstiukAE

CapiniC

L'HeureuxD

2001 CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia: perivascular accumulation and reservoir of HIV infection. J Neurovirol 7 528 541

26. KimWK

AvarezX

WilliamsK

2005 The role of monocytes and perivascular macrophages in HIV and SIV neuropathogenesis: information from non-human primate models. Neurotox Res 8 107 115

27. KimWK

CoreyS

AlvarezX

WilliamsK

2003 Monocyte/macrophage traffic in HIV and SIV encephalitis. J Leukoc Biol 74 650 656

28. WilliamsKC

HickeyWF

1995 Traffic of hematogenous cells through the central nervous system. Curr Top Microbiol Immunol 202 221 245

29. KedzierskaK

CroweSM

2002 The role of monocytes and macrophages in the pathogenesis of HIV-1 infection. Curr Med Chem 9 1893 1903

30. PulliamL

GasconR

StubblebineM

McGuireD

McGrathMS

1997 Unique monocyte subset in patients with AIDS dementia. Lancet 349 692 695

31. ThieblemontN

WeissL

SadeghiHM

EstcourtC

Haeffner-CavaillonN

1995 CD14lowCD16high: a cytokine-producing monocyte subset which expands during human immunodeficiency virus infection. Eur J Immunol 25 3418 3424

32. WilliamsK

WestmorelandS

GrecoJ

RataiE

LentzM

2005 Magnetic resonance spectroscopy reveals that activated monocytes contribute to neuronal injury in SIV neuroAIDS. J Clin Invest 115 2534 2545

33. WilliamsKC

CoreyS

WestmorelandSV

PauleyD

KnightH

2001 Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: implications for the neuropathogenesis of AIDS. J Exp Med 193 905 915

34. WilliamsK

SchwartzA

CoreyS

OrandleM

KennedyW

2002 Proliferating cellular nuclear antigen expression as a marker of perivascular macrophages in simian immunodeficiency virus encephalitis. Am J Pathol 161 575 585

35. WilliamsKC

HickeyWF

2002 Central nervous system damage, monocytes and macrophages, and neurological disorders in AIDS. Annu Rev Neurosci 25 537 562

36. SchmitzJE

SimonMA

KurodaMJ

LiftonMA

OllertMW

1999 A nonhuman primate model for the selective elimination of CD8+ lymphocytes using a mouse-human chimeric monoclonal antibody. Am J Pathol 154 1923 1932

37. SchmitzJE

JohnsonRP

McClureHM

MansonKH

WyandMS

2005 Effect of CD8+ lymphocyte depletion on virus containment after simian immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239delta3-vaccinated rhesus macaques. J Virol 79 8131 8141

38. SchmitzJE

KurodaMJ

SantraS

SassevilleVG

SimonMA

1999 Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283 857 860

39. DavisBH

ZarevPV

2005 Human monocyte CD163 expression inversely correlates with soluble CD163 plasma levels. Cytometry B Clin Cytom 63 16 22

40. MollerHJ

PeterslundNA

GraversenJH

MoestrupSK

2002 Identification of the hemoglobin scavenger receptor/CD163 as a natural soluble protein in plasma. Blood 99 378 380

41. BuechlerC

RitterM

OrsoE

LangmannT

KluckenJ

2000 Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli. J Leukoc Biol 67 97 103

42. FabriekBO

DijkstraCD

van den BergTK

2005 The macrophage scavenger receptor CD163. Immunobiology 210 153 160

43. KimWK

AlvarezX

FisherJ

BronfinB

WestmorelandS

2006 CD163 identifies perivascular macrophages in normal and viral encephalitic brains and potential precursors to perivascular macrophages in blood. Am J Pathol 168 822 834

44. MoestrupSK

MollerHJ

2004 CD163: a regulated hemoglobin scavenger receptor with a role in the anti-inflammatory response. Ann Med 36 347 354

45. WeaverLK

Hintz-GoldsteinKA

PioliPA

WardwellK

QureshiN

2006 Pivotal advance: activation of cell surface Toll-like receptors causes shedding of the hemoglobin scavenger receptor CD163. J Leukoc Biol 80 26 35

46. CordoneI

MatutesE

CatovskyD

1992 Characterisation of normal peripheral blood cells in cycle identified by monoclonal antibody Ki-67. J Clin Pathol 45 201 205

47. GoudTJ

van FurthR

1975 Proliferative characteristics of monoblasts grown in vitro. J Exp Med 142 1200 1217

48. van FurthR

RaeburnJA

van ZwetTL

1979 Characteristics of human mononuclear phagocytes. Blood 54 485 500

49. GerdesJ

LemkeH

BaischH

WackerHH

SchwabU

1984 Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133 1710 1715

50. PasslickB

FliegerD

Ziegler-HeitbrockHW

1989 Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood 74 2527 2534

51. MarcondesMC

LaniganCM

BurdoTH

WatryDD

FoxHS

2008 Increased expression of monocyte CD44v6 correlates with the deveopment of encephalitis in rhesus macaques infected with simian immunodeficiency virus. J Infect Dis 197 1567 1576

52. BrenchleyJM

PriceDA

SchackerTW

AsherTE

SilvestriG

2006 Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12 1365 1371

53. AncutaP

KamatA

KunstmanKJ

KimEY

AutissierP

2008 Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS ONE 3 e2516 doi:10.1371/journal.pone.0002516

54. FabriekBO

Van HaastertES

GaleaI

PolflietMM

DoppED

2005 CD163-positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation. Glia 51 297 305

55. WeaverLK

PioliPA

WardwellK

VogelSN

GuyrePM

2007 Up-regulation of human monocyte CD163 upon activation of cell-surface Toll-like receptors. J Leukoc Biol 81 663 671

56. BruckW

PoradaP

PoserS

RieckmannP

HanefeldF

1995 Monocyte/macrophage differentiation in early multiple sclerosis lesions. Ann Neurol 38 788 796

57. OtaniI

MoriK

SataT

TeraoK

DoiK

1999 Accumulation of MAC387+ macrophages in paracortical areas of lymph nodes in rhesus monkeys acutely infected with simian immunodeficiency virus. Microbes Infect 1 977 985

58. RaginAB

WuY

StoreyP

CohenBA

EdelmanRR

2006 Bone marrow diffusion measures correlate with dementia severity in HIV patients. AJNR Am J Neuroradiol 27 589 592

59. WestmorelandSV

HalpernE

LacknerAA

1998 Simian immunodeficiency virus encephalitis in rhesus macaques is associated with rapid disease progression. J Neurovirol 4 260 268

60. MollerHJ

de FostM

AertsH

HollakC

MoestrupSK

2004 Plasma level of the macrophage-derived soluble CD163 is increased and positively correlates with severity in Gaucher's disease. Eur J Haematol 72 135 139

61. GiriMS

NebozyhnM

RaymondA

GekongeB

HancockA

2009 Circulating monocytes in HIV-1-infected viremic subjects exhibit an antiapoptosis gene signature and virus- and host-mediated apoptosis resistance. J Immunol 182 4459 4470

62. SerbinaNV

PamerEG

2006 Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 7 311 317

63. TsouCL

PetersW

SiY

SlaymakerS

AslanianAM

2007 Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites. J Clin Invest 117 902 909

64. LapidotT

PetitI

2002 Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp Hematol 30 973 981

65. PeledA

PetitI

KolletO

MagidM

PonomaryovT

1999 Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 283 845 848

66. AncutaP

LiuKY

MisraV

WaclecheVS

GosselinA

2009 Transcriptional profiling reveals developmental relationship and distinct biological functions of CD16+ and CD16- monocyte subsets. BMC Genomics 10 403

67. KomoharaY

HiraharaJ

HorikawaT

KawamuraK

KiyotaE

2006 AM-3K, an anti-macrophage antibody, recognizes CD163, a molecule associated with an anti-inflammatory macrophage phenotype. J Histochem Cytochem 54 763 771

68. SassevilleVG

LacknerAA

1997 Neuropathogenesis of simian immunodeficiency virus infection in macaque monkeys. J Neurovirol 3 1 9

69. NathA

1999 Pathobiology of human immunodeficiency virus dementia. Semin Neurol 19 113 127

70. BellJE

1998 The neuropathology of adult HIV infection. Rev Neurol (Paris) 154 816 829

71. LifsonJD

RossioJL

PiatakMJr

ParksT

LiL

2001 Role of CD8(+) lymphocytes in control of simian immunodeficiency virus infection and resistance to rechallenge after transient early antiretroviral treatment. J Virol 75 10187 10199

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