Human Macrophage Responses to Clinical Isolates from the Complex Discriminate between Ancient and Modern Lineages


The aim of the present study was to determine whether there is a correlation between phylogenetic relationship and inflammatory response amongst a panel of clinical isolates representative of the global diversity of the human Mycobacterium tuberculosis Complex (MTBC). Measurement of cytokines from infected human peripheral blood monocyte-derived macrophages revealed a wide variation in the response to different strains. The same pattern of high or low response to individual strains was observed for different pro-inflammatory cytokines and chemokines, and was conserved across multiple human donors. Although each major phylogenetic lineage of MTBC included strains inducing a range of cytokine responses, we found that overall inflammatory phenotypes differed significantly across lineages. In particular, comparison of evolutionarily modern lineages demonstrated a significant skewing towards lower early inflammatory response. The differential response to ancient and modern lineages observed using GM-CSF derived macrophages was also observed in autologous monocyte-derived dendritic cells and murine bone marrow-derived macrophages, but not in human unfractionated peripheral blood mononuclear cells. We hypothesize that the reduced immune responses to modern lineages contribute to more rapid disease progression and transmission, which might be a selective advantage in the context of expanding human populations. In addition to the lineage effects, the large strain-to-strain variation in innate immune responses elicited by MTBC will need to be considered in tuberculosis vaccine development.


Vyšlo v časopise: Human Macrophage Responses to Clinical Isolates from the Complex Discriminate between Ancient and Modern Lineages. PLoS Pathog 7(3): e32767. doi:10.1371/journal.ppat.1001307
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001307

Souhrn

The aim of the present study was to determine whether there is a correlation between phylogenetic relationship and inflammatory response amongst a panel of clinical isolates representative of the global diversity of the human Mycobacterium tuberculosis Complex (MTBC). Measurement of cytokines from infected human peripheral blood monocyte-derived macrophages revealed a wide variation in the response to different strains. The same pattern of high or low response to individual strains was observed for different pro-inflammatory cytokines and chemokines, and was conserved across multiple human donors. Although each major phylogenetic lineage of MTBC included strains inducing a range of cytokine responses, we found that overall inflammatory phenotypes differed significantly across lineages. In particular, comparison of evolutionarily modern lineages demonstrated a significant skewing towards lower early inflammatory response. The differential response to ancient and modern lineages observed using GM-CSF derived macrophages was also observed in autologous monocyte-derived dendritic cells and murine bone marrow-derived macrophages, but not in human unfractionated peripheral blood mononuclear cells. We hypothesize that the reduced immune responses to modern lineages contribute to more rapid disease progression and transmission, which might be a selective advantage in the context of expanding human populations. In addition to the lineage effects, the large strain-to-strain variation in innate immune responses elicited by MTBC will need to be considered in tuberculosis vaccine development.


Zdroje

1. HershbergR

LipatovM

SmallPM

ShefferH

NiemannS

2008 High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography. PLoS Biol 6 e311

2. ComasI

ChakravarttiJ

SmallPM

GalaganJ

NiemannS

2010 Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved. Nat Genet 42 498 503

3. de JongBC

AntonioM

GagneuxS

2010 Mycobacterium africanum review of an important cause of human tuberculosis in West Africa. PLoS Negl Trop Dis 4 e744

4. GagneuxS

SmallPM

2007 Global phylogeography of Mycobacterium tuberculosis and implications for tuberculosis product development. Lancet Infect Dis 7 328 337

5. NicolMP

WilkinsonRJ

2008 The clinical consequences of strain diversity in Mycobacterium tuberculosis. Trans R Soc Trop Med Hyg 102 955 965

6. CoscollaM

GagneuxS

2010 Does M. tuberculosis genomic diversity explain disease diversity? Drug Discov Today: Dis Mech 7 e43 e59

7. CawsM

ThwaitesG

DunstanS

HawnTR

LanNT

2008 The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis. PLoS Pathog 4 e1000034

8. KongY

CaveMD

ZhangL

FoxmanB

MarrsCF

2007 Association between Mycobacterium tuberculosis Beijing/W lineage strain infection and extrathoracic tuberculosis: Insights from epidemiologic and clinical characterization of the three principal genetic groups of M. tuberculosis clinical isolates. J Clin Microbiol 45 409 414

9. RakotosamimananaN

RaharimangaV

AndriamandimbySF

SoaresJL

DohertyTM

2010 Variation in IFN-{gamma} responses to different infecting strains of Mycobacterium tuberculosis in AFB smear positive patients and household contacts in Antananarivo, Madagascar. Clin Vaccine Immunol 17 1094 1103

10. MancaC

ReedMB

FreemanS

MathemaB

KreiswirthB

2004 Differential monocyte activation underlies strain-specific Mycobacterium tuberculosis pathogenesis. Infect Immun 72 5511 5514

11. ReedMB

DomenechP

MancaC

SuH

BarczakAK

2004 A glycolipid of hypervirulent tuberculosis strains that inhibits the innate immune response. Nature 431 84 87

12. TanveerM

HasanZ

KanjiA

HussainR

HasanR

2009 Reduced TNF-alpha and IFN-gamma responses to Central Asian strain 1 and Beijing isolates of Mycobacterium tuberculosis in comparison with H37Rv strain. Trans R Soc Trop Med Hyg 103 581 587

13. LopezB

AguilarD

OrozcoH

BurgerM

EspitiaC

2003 A marked difference in pathogenesis and immune response induced by different Mycobacterium tuberculosis genotypes. Clin Exp Immunol 133 30 37

14. HanekomM

van der SpuyGD

StreicherE

NdabambiSL

McEvoyCR

2007 A recently evolved sublineage of the Mycobacterium tuberculosis Beijing strain family is associated with an increased ability to spread and cause disease. J Clin Microbiol 45 1483 1490

15. NewtonSM

SmithRJ

WilkinsonKA

NicolMP

GartonNJ

2006 A deletion defining a common Asian lineage of Mycobacterium tuberculosis associates with immune subversion. Proc Natl Acad Sci U S A 103 15594 15598

16. SinsimerD

HuetG

MancaC

TsenovaL

KooMS

2008 The phenolic glycolipid of Mycobacterium tuberculosis differentially modulates the early host cytokine response but does not in itself confer hypervirulence. Infect Immun 76 3027 3036

17. Marquina-CastilloB

Garcia-GarciaL

Ponce-de-LeonA

Jimenez-CoronaME

Bobadilla-Del ValleM

2009 Virulence, immunopathology and transmissibility of selected strains of Mycobacterium tuberculosis in a murine model. Immunology 128 123 133

18. Hoal-van HeldenEG

StantonLA

WarrenR

RichardsonM

van HeldenPD

2001 Diversity of in vitro cytokine responses by human macrophages to infection by Mycobacterium tuberculosis strains. Cell Biol Int 25 83 90

19. TheusSA

CaveMD

EisenachKD

2005 Intracellular macrophage growth rates and cytokine profiles of Mycobacterium tuberculosis strains with different transmission dynamics. J Infect Dis 191 453 460

20. GagneuxS

DeRiemerK

VanT

Kato-MaedaM

de JongBC

2006 Variable host-pathogen compatibility in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 103 2869 2873

21. VerreckFA

de BoerT

LangenbergDM

HoeveMA

KramerM

2004 Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria. Proc Natl Acad Sci U S A 101 4560 4565

22. BroschR

GordonSV

MarmiesseM

BrodinP

BuchrieserC

2002 A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc Natl Acad Sci U S A 99 3684 3689

23. de Waal MalefytR

AbramsJ

BennettB

FigdorCG

de VriesJE

1991 Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 174 1209 1220

24. SaraivaM

O'GarraA

2010 The regulation of IL-10 production by immune cells. Nat Rev Immunol 10 170 181

25. IshikawaE

IshikawaT

MoritaYS

ToyonagaK

YamadaH

2009 Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J Exp Med 206 2879 2888

26. StewartGR

WilkinsonKA

NewtonSM

SullivanSM

NeyrollesO

2005 Effect of deletion or overexpression of the 19-kilodalton lipoprotein Rv3763 on the innate response to Mycobacterium tuberculosis. Infect Immun 73 6831 6837

27. NigouJ

VasselonT

RayA

ConstantP

GilleronM

2008 Mannan chain length controls lipoglycans signaling via and binding to TLR2. J Immunol 180 6696 6702

28. RaoV

FujiwaraN

PorcelliSA

GlickmanMS

2005 Mycobacterium tuberculosis controls host innate immune activation through cyclopropane modification of a glycolipid effector molecule. J Exp Med 201 535 543

29. JoEK

2008 Mycobacterial interaction with innate receptors: TLRs, C-type lectins, and NLRs. Curr Opin Infect Dis 21 279 286

30. BlaserMJ

KirschnerD

2007 The equilibria that allow bacterial persistence in human hosts. Nature 449 843 849

31. SmithNH

HewinsonRG

KremerK

BroschR

GordonSV

2009 Myths and misconceptions: the origin and evolution of Mycobacterium tuberculosis. Nat Rev Microbiol 7 537 544

32. de JongBC

HillPC

AikenA

AwineT

AntonioM

2008 Progression to active tuberculosis, but not transmission, varies by Mycobacterium tuberculosis lineage in The Gambia. J Infect Dis 198 1037 1043

33. KeatingLA

WheelerPR

MansoorH

InwaldJK

DaleJ

2005 The pyruvate requirement of some members of the Mycobacterium tuberculosis complex is due to an inactive pyruvate kinase: implications for in vivo growth. Mol Microbiol 56 163 174

34. N'DiayeEN

DarzacqX

Astarie-DequekerC

DaffeM

CalafatJ

1998 Fusion of azurophil granules with phagosomes and activation of the tyrosine kinase Hck are specifically inhibited during phagocytosis of mycobacteria by human neutrophils. J Immunol 161 4983 4991

35. ContiL

CardoneM

VaranoB

PudduP

BelardelliF

2008 Role of the cytokine environment and cytokine receptor expression on the generation of functionally distinct dendritic cells from human monocytes. Eur J Immunol 38 750 762

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2011 Číslo 3
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Eozinofilní granulomatóza s polyangiitidou
nový kurz
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa