A Mouse Model of Lethal Synergism Between Influenza Virus and Haemophilus influenzae

被引:50
作者
Lee, Lian Ni [1 ]
Dias, Peter [1 ]
Han, Dongun [1 ]
Yoon, Sorah [1 ]
Shea, Ashley [1 ]
Zakharov, Vladislav [2 ]
Parham, David [2 ]
Sarawar, Sally R. [1 ]
机构
[1] Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA
[2] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA
基金
美国国家卫生研究院;
关键词
OBSTRUCTIVE PULMONARY-DISEASE; A H5N1 VIRUSES; STREPTOCOCCUS-PNEUMONIAE; BACTERIAL PNEUMONIA; INFLAMMATORY RESPONSE; EPITHELIAL-CELLS; INFECTION; MICE; LIPOPOLYSACCHARIDE; SUPERINFECTION;
D O I
10.2353/ajpath.2010.090596
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Secondary bacterial infections that follow infection with influenza virus result in considerable morbidity and mortality in young children, the elderly, and immunocompromised individuals and may also significantly increase mortality in normal healthy adults during influenza pandemics. We herein describe a mouse model for investigating the interaction between influenza virus and the bacterium Haemophilus influenzae. Sequential infection with sublethal doses of influenza and H. influenzae resulted in synergy between the two pathogens and caused mortality in immunocompetent adult wild-type mice. Lethality was dependent on the interval between administration of the bacteria and virus, and bacterial growth was prolonged in the lungs of dual-infected mice, although influenza virus titers were unaffected. Dual infection induced severe damage to the airway epithelium and confluent pneumonia, similar to that observed in victims of the 1918 global influenza pandemic. Increased bronchial epithelial cell death was observed as early as I day after bacterial inoculation in the dual-infected mice. Studies using knockout mice indicated that lethality occurs via a mechanism that is not dependent on Fas, CCR2, CXCR3, interleukin-6, tumor necrosis factor, or Toll-like receptor-4 and does not require T or B cells. This model suggests that infection with virulent strains of influenza may predispose even immunocompetent individuals to severe illness on secondary infection with H. influenzae by a mechanism that involves innate immunity, but does not require tumor necrosis factor, interleukin-6, or signaling via Toll-like receptor-4. (Am J Pathol 2010, 176:800-811; DOI: 10.2353/ajpath.2010.090596)
引用
收藏
页码:800 / 811
页数:12
相关论文
共 93 条
[1]   A model of meningococcal bacteremia after respiratory superinfection in influenza A virus-infected mice [J].
Alonso, JM ;
Guiyoule, A ;
Zarantonelli, ML ;
Ramisse, F ;
Pires, R ;
Aude, A ;
Deghmane, AE ;
Huerre, M ;
van der Werf, S ;
Taha, MK .
FEMS MICROBIOLOGY LETTERS, 2003, 222 (01) :99-106
[2]  
[Anonymous], ANTHR PROC MAN NAT H
[3]  
Aubrey Ruth, 2003, Methods Mol Med, V71, P29
[4]   THE EFFECT OF ANTECEDENT INFLUENZA-A VIRUS-INFECTION ON THE ADHERENCE OF HEMOPHILUS-INFLUENZAE TO CHINCHILLA TRACHEAL EPITHELIUM [J].
BAKALETZ, LO ;
HOEPF, TM ;
DEMARIA, TF ;
LIM, DJ .
AMERICAN JOURNAL OF OTOLARYNGOLOGY, 1988, 9 (03) :127-134
[5]   Identification of Toll-like receptor 4 (Tlr4) as the sole conduit for LPS signal transduction: genetic and evolutionary studies [J].
Beutler, B ;
Du, X ;
Poltorak, A .
JOURNAL OF ENDOTOXIN RESEARCH, 2001, 7 (04) :277-280
[6]  
Bröker M, 2009, JPN J INFECT DIS, V62, P87
[7]   Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness [J].
Brundage, JF .
LANCET INFECTIOUS DISEASES, 2006, 6 (05) :303-312
[8]   Deaths from bacterial pneumonia during 1918-19 influenza pandemic [J].
Brundage, John F. ;
Shanks, G. Dennis .
EMERGING INFECTIOUS DISEASES, 2008, 14 (08) :1193-1199
[9]   What really happened during the 1918 influenza pandemic? The importance of bacterial secondary infections [J].
Brundage, John F. ;
Shanks, G. Dennis .
JOURNAL OF INFECTIOUS DISEASES, 2007, 196 (11) :1717-1718
[10]   Cases and deaths during influenza pandemics in the United States [J].
Brundage, John F. .
AMERICAN JOURNAL OF PREVENTIVE MEDICINE, 2006, 31 (03) :252-256