M2 Polarization of Human Macrophages Favors Survival of the Intracellular Pathogen Chlamydia pneumoniae

被引:100
作者
Buchacher, Tanja [1 ]
Ohradanova-Repic, Anna [2 ]
Stockinger, Hannes [2 ]
Fischer, Michael B. [3 ,4 ]
Weber, Viktoria [1 ,4 ]
机构
[1] Danube Univ Krems, Christian Doppler Lab Innovat Therapy Approaches, Krems, Austria
[2] Med Univ Vienna, Ctr Pathophysiol Infectiol & Immunol, Inst Hyg & Appl Immunol, Mol Immunol Unit, Vienna, Austria
[3] Med Univ Vienna, Dept Blood Grp Serol & Transfus Med, Vienna, Austria
[4] Danube Univ Krems, Dept Hlth Sci & Biomed, Krems, Austria
关键词
FRANCISELLA-TULARENSIS REPLICATION; HUMAN BLOOD MONOCYTES; IFN-GAMMA; IN-VITRO; M-CSF; INFECTION; CELLS; TRACHOMATIS; ACTIVATION; PERSISTENCE;
D O I
10.1371/journal.pone.0143593
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Intracellular pathogens have developed various strategies to escape immunity to enable their survival in host cells, and many bacterial pathogens preferentially reside inside macrophages, using diverse mechanisms to penetrate their defenses and to exploit their high degree of metabolic diversity and plasticity. Here, we characterized the interactions of the intracellular pathogen Chlamydia pneumoniae with polarized human macrophages. Primary human monocytes were pre-differentiated with granulocyte macrophage colony-stimulating factor or macrophage colony-stimulating factor for 7 days to yield M1-like and M2-like macrophages, which were further treated with interferon-gamma and lipopolysaccharide or with interleukin-4 for 48 h to obtain fully polarized M1 and M2 macrophages. M1 and M2 cells exhibited distinct morphology with round or spindle-shaped appearance for M1 and M2, respectively, distinct surface marker profiles, as well as different cytokine and chemokine secretion. Macrophage polarization did not influence uptake of C. pneumoniae, since comparable copy numbers of chlamydial DNA were detected in M1 and M2 at 6 h post infection, but an increase in chlamydial DNA over time indicating proliferation was only observed in M2. Accordingly, 72 +/- 5% of M2 vs. 48 +/- 7% of M1 stained positive for chlamydial lipopolysaccharide, with large perinuclear inclusions in M2 and less clearly bordered inclusions for M1. Viable C. pneumoniae was present in lysates from M2, but not from M1 macrophages. The ability of M1 to restrict chlamydial replication was not observed in M1-like macrophages, since chlamydial load showed an equal increase over time for M1-like and M2-like macrophages. Our findings support the importance of macrophage polarization for the control of intracellular infection, and show that M2 are the preferred survival niche for C. pneumoniae. M1 did not allow for chlamydial proliferation, but failed to completely eliminate chlamydial infection, giving further evidence for the ability of C. pneumoniae to evade cellular defense and to persist in human macrophages.
引用
收藏
页数:16
相关论文
共 42 条
[1]   Lack of PPARγ in Myeloid Cells Confers Resistance to Listeria monocytogenes Infection [J].
Abdullah, Zeinab ;
Geiger, Sergej ;
Nino-Castro, Andrea ;
Boettcher, Jan P. ;
Muraliv, Eugenia ;
Gaidt, Moritz ;
Schildberg, Frank A. ;
Riethausen, Kati ;
Flossdorf, Juliane ;
Krebs, Wolfgang ;
Chakraborty, Trinad ;
Kurts, Christian ;
Schultze, Joachim L. ;
Knolle, Percy A. ;
Klotz, Luisa .
PLOS ONE, 2012, 7 (05)
[2]   Chlamydia pneumoniae infection in human monocytes [J].
Airenne, S ;
Surcel, HM ;
Alakärppä, H ;
Laitinen, K ;
Paavonen, J ;
Saikku, P ;
Laurila, A .
INFECTION AND IMMUNITY, 1999, 67 (03) :1445-1449
[3]  
Balin BJ, 2008, J ALZHEIMERS DIS, V13, P371
[4]   Macrophage polarization in bacterial infections [J].
Benoit, Marie ;
Desnues, Benoit ;
Mege, Jean-Louis .
JOURNAL OF IMMUNOLOGY, 2008, 181 (06) :3733-3739
[5]   Orchestration of Metabolism by Macrophages [J].
Biswas, Subhra K. ;
Mantovani, Alberto .
CELL METABOLISM, 2012, 15 (04) :432-437
[6]   Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm [J].
Biswas, Subhra K. ;
Mantovani, Alberto .
NATURE IMMUNOLOGY, 2010, 11 (10) :889-896
[7]   Human blood monocytes support persistence, but not replication of the intracellular pathogen C. pneumoniae [J].
Buchacher, Tanja ;
Wiesinger-Mayr, Herbert ;
Vierlinger, Klemens ;
Rueger, Beate M. ;
Stanek, Gerold ;
Fischer, Michael B. ;
Weber, Viktoria .
BMC IMMUNOLOGY, 2014, 15
[8]   New insights into Chlamydia intracellular survival mechanisms [J].
Cocchiaro, Jordan L. ;
Valdivia, Raphael H. .
CELLULAR MICROBIOLOGY, 2009, 11 (11) :1571-1578
[9]   Differential infection outcome of Chlamydia trachomatis in human blood monocytes and monocyte-derived dendritic cells [J].
Datta, Baishakhi ;
Njau, Florence ;
Thalmann, Jessica ;
Haller, Hermann ;
Wagner, Annette D. .
BMC MICROBIOLOGY, 2014, 14
[10]   Unravelling mononuclear phagocyte heterogeneity [J].
Geissmann, Frederic ;
Gordon, Siamon ;
Hume, David A. ;
Mowat, Allan M. ;
Randolph, Gwendalyn J. .
NATURE REVIEWS IMMUNOLOGY, 2010, 10 (06) :453-U92