TLR2, but Not TLR4, Is Required for Effective Host Defence against Chlamydia Respiratory Tract Infection in Early Life

被引:56
作者
Beckett, Emma L. [1 ,2 ]
Phipps, Simon [3 ,4 ]
Starkey, Malcolm R. [1 ,2 ]
Horvat, Jay C. [1 ,2 ]
Beagley, Kenneth W. [5 ]
Foster, Paul S. [1 ,2 ]
Hansbro, Philip M. [1 ,2 ]
机构
[1] Univ Newcastle, Ctr Asthma & Resp Dis, Newcastle, NSW 2300, Australia
[2] Hunter Med Res Inst, Newcastle, NSW 2300, Australia
[3] Univ Queensland, Australian Infect Dis Res Ctr, Brisbane, Qld, Australia
[4] Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia
[5] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia
基金
英国医学研究理事会;
关键词
ALLERGIC AIRWAYS DISEASE; MYELOID DENDRITIC CELLS; TRANSCUTANEOUS IMMUNIZATION; PNEUMONIAE INFECTION; MURIDARUM INFECTION; PROTECTIVE IMMUNITY; TH2; IMMUNITY; RECEPTOR; INDUCTION; ASTHMA;
D O I
10.1371/journal.pone.0039460
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
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Chlamydia pneumoniae commonly causes respiratory tract infections in children, and epidemiological investigations strongly link infection to the pathogenesis of asthma. The immune system in early life is immature and may not respond appropriately to pathogens. Toll-like receptor (TLR)2 and 4 are regarded as the primary pattern recognition receptors that sense bacteria, however their contribution to innate and adaptive immunity in early life remains poorly defined. We investigated the role of TLR2 and 4 in the induction of immune responses to Chlamydia muridarum respiratory infection, in neonatal wild-type (Wt) or TLR2-deficient ((-/-)), 4(-/-) or 2/4(-/-) BALB/c mice. Wt mice had moderate disease and infection. TLR2(-/-) mice had more severe disease and more intense and prolonged infection compared to other groups. TLR4(-/-) mice were asymptomatic. TLR2/4(-/-) mice had severe early disease and persistent infection, which resolved thereafter consistent with the absence of symptoms in TLR4(-/-) mice. Wt mice mounted robust innate and adaptive responses with an influx of natural killer (NK) cells, neutrophils, myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells, and activated CD4(+) and CD8(+) T-cells into the lungs. Wt mice also had effective production of interferon (IFN)gamma in the lymph nodes and lung, and proliferation of lymph node T-cells. TLR2(-/-) mice had more intense and persistent innate (particularly neutrophil) and adaptive cell responses and IL-17 expression in the lung, however IFN gamma responses and T-cell proliferation were reduced. TLR2/4(-/-) mice had reduced innate and adaptive responses. Most importantly, neutrophil phagocytosis was impaired in the absence of TLR2. Thus, TLR2 expression, particularly on neutrophils, is required for effective control of Chlamydia respiratory infection in early life. Loss of control of infection leads to enhanced but ineffective TLR4-mediated inflammatory responses that prolong disease symptoms. This indicates that TLR2 agonists may be beneficial in the treatment of early life Chlamydia infections and associated diseases.
引用
收藏
页数:13
相关论文
共 56 条
[1]
The generation of th memory in neonates versus adults: Prolonged primary Th2 effector function and impaired development of Th1 memory effector function in murine neonates [J].
Adkins, P ;
Bu, YR ;
Guevara, P .
JOURNAL OF IMMUNOLOGY, 2001, 166 (02) :918-925
[2]
Toll-like receptor signalling [J].
Akira, S ;
Takeda, K .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (07) :499-511
[3]
The IL-3/IL-5/GM-CSF common β receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation [J].
Asquith, Kelly L. ;
Ramshaw, Hayley S. ;
Hansbro, Philip M. ;
Beagley, Kenneth W. ;
Lopez, Angel F. ;
Foster, Paul S. .
JOURNAL OF IMMUNOLOGY, 2008, 180 (02) :1199-1206
[4]
Interleukin-13 Promotes Susceptibility to Chlamydial Infection of the Respiratory and Genital Tracts [J].
Asquith, Kelly L. ;
Horvat, Jay C. ;
Kaiko, Gerard E. ;
Carey, Alison J. ;
Beagley, Kenneth W. ;
Hansbro, Philip M. ;
Foster, Paul S. .
PLOS PATHOGENS, 2011, 7 (05)
[5]
Chlamydial Infection of Immune Cells: Altered Function and Implications for Disease [J].
Beagley, Kenneth W. ;
Huston, Wilhelmina M. ;
Hansbro, Philip M. ;
Timms, Peter .
CRITICAL REVIEWS IN IMMUNOLOGY, 2009, 29 (04) :275-305
[6]
Chlamydia pneumoniae and atherosclerosis [J].
Belland, RJ ;
Ouellette, SP ;
Gieffers, J ;
Byrne, GI .
CELLULAR MICROBIOLOGY, 2004, 6 (02) :117-127
[7]
Transcutaneous immunization with combined cholera toxin and CpG adjuvant protects against Chlamydia muridarum genital tract infection [J].
Berry, LJ ;
Hickey, DK ;
Skelding, KA ;
Bao, S ;
Rendina, AM ;
Hansbro, PM ;
Gockel, CM ;
Beagley, KW .
INFECTION AND IMMUNITY, 2004, 72 (02) :1019-1028
[8]
Chlamydia pneumoniae respiratory infections [J].
Blasi, F ;
Cosentini, R ;
Tarsia, P .
CURRENT OPINION IN INFECTIOUS DISEASES, 2000, 13 (02) :161-164
[9]
A TLR2 agonist is a more effective adjuvant for a Chlamydia major outer membrane protein vaccine than ligands to other TLR and NOD receptors [J].
Cheng, Chunmei ;
Jain, Pooja ;
Bettahi, Ilham ;
Pal, Sukumar ;
Tifrea, Delia ;
de la Maza, Luis M. .
VACCINE, 2011, 29 (38) :6641-6649
[10]
Age at first viral infection determines the pattern of T cell-mediated disease during reinfection in adulthood [J].
Culley, FJ ;
Pollott, J ;
Openshaw, PJM .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (10) :1381-1386