Potter, C. W. in Textbook of Influenza (eds Nicholson, K. G., Webster, R. G. and Hay, A. J.) 3–18 (Blackwell Scientific Publications, 1998).
Morens, D. M., Taubenberger, J. K. & Fauci, A. S. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J. Infect. Dis. 198, 962–970 (2008).
This paper presents a comprehensive review of the aetiology of fatal cases during the 1918 pandemic.
Smith, A. M. & McCullers, J. A. Molecular signatures of virulence in the PB1-F2 proteins of H5N1 influenza viruses. Virus Res. 178, 146–150 (2013).
Collins, S. D. Influenza–pneumonia mortality in a group of about 95 cities in the United States, 1920–1929. Public Health Rep. 45, 361–406 (1930).
van Asten, L. et al. Mortality attributable to 9 common infections: significant effect of influenza A, respiratory syncytial virus, influenza B, norovirus, and parainfluenza in elderly persons. J. Infect. Dis. 206, 628–639 (2012).
Nolte, F. S. Molecular diagnostics for detection of bacterial and viral pathogens in community-acquired pneumonia. Clin. Infect. Dis. 47, S123–S126 (2008).
Weinberger, D. M. et al. Impact of the 2009 influenza pandemic on pneumococcal pneumonia hospitalizations in the United States. J. Infect. Dis. 205, 458–465 (2012).
Falsey, A. R. et al. Bacterial complications of respiratory tract viral illness: a comprehensive evaluation. J. Infect. Dis. 208, 432–441 (2013).
This recent paper documents a high rate of co-infections in a large study of hospitalized patients with pneumonia.
McCullers, J. A. Do specific virus–bacteria pairings drive clinical outcomes of pneumonia? Clin. Microbiol. Infect. 19, 113–118 (2013).
Brundage, J. F. & Shanks, G. D. What really happened during the 1918 influenza pandemic? The importance of bacterial secondary infections. J. Infect. Dis. 196, 1717–1718 (2007).
Chien, Y. W., Klugman, K. P. & Morens, D. M. Bacterial pathogens and death during the 1918 influenza pandemic. N. Engl. J. Med. 361, 2582–2583 (2009).
Brundage, J. F. & Shanks, G. D. Deaths from bacterial pneumonia during 1918–1919 influenza pandemic. Emerg. Infect. Dis. 14, 1193–1199 (2008).
Shanks, G. D. et al. Mortality risk factors during the 1918–1919 influenza pandemic in the Australian army. J. Infect. Dis. 201, 1880–1889 (2010).
Shanks, G. D., MacKenzie, A., Waller, M. & Brundage, J. F. Low but highly variable mortality among nurses and physicians during the influenza pandemic of 1918–1919. Influenza Other Respir. Viruses 5, 213–219 (2011).
Jordan, E. O. in Epidemic Influenza 356–438 (American Medical Association, 1927).
This comprehensive and historically important textbook explores all aspects of influenza epidemiology and research in the nineteenth and early twentieth centuries.
Trotter, Y. Jr et al. Asian influenza in the United States, 1957–1958. Am. J. Hyg. 70, 34–50 (1959).
Dauer, C. C. Mortality in the 1957–1958 influenza epidemic. Public Health Rep. 73, 803–810 (1958).
Collins, S. D. & Lehmann, J. Trends and epidemics of influenza and pneumonia: 1918–1951. Public Health Rep. 66, 1487–1516 (1951).
Giles, C. & Shuttleworth, E. M. Postmortem findings in 46 influenza deaths. Lancet 273, 1224–1225 (1957).
Martin, C. M., Kunin, C. M., Gottlieb, L. S. & Finland, M. Asian influenza A in Boston, 1957–1958. II. Severe staphylococcal pneumonia complicating influenza. AMA. Arch. Intern. Med. 103, 532–542 (1959).
Oseasohn, R., Adelson, L. & Kaji, M. Clinicopathologic study of thirty-three fatal cases of Asian influenza. N. Engl. J. Med. 260, 509–518 (1959).
Hers, J. F. P., Masurel, N. & Mulder, J. Bacteriology and histopathology of the respiratory tract and lungs of fatal Asian influenza. Lancet 2, 1164–1165 (1958).
Hers, J. F., Goslings, W. R., Masurel, N. & Mulder, J. Death from Asiatic influenza in the Netherlands. Lancet 273, 1164–1165 (1957).
Robertson, L., Caley, J. P. & Moore, J. Importance of Staphylococcus aureus in pneumonia in the 1957 epidemic of influenza A. Lancet 2, 233–236 (1958).
Herzog, H., Staub, H. & Richterich, R. Gas-analytical studies in severe pneumonia; observations during the 1957 influenza epidemic. Lancet 1, 593–597 (1959).
Jevons, M. P., Taylor, C. E. D. & Williams, R. E. O. Bacteria and influenza. Lancet 273, 835–836 (1957).
Schwarzmann, S. W., Adler, J. L., Sullivan, R. J. Jr. & Marine, W. M. Bacterial pneumonia during the Hong Kong influenza epidemic of 1968–1969. Arch. Intern. Med. 127, 1037–1041 (1971).
Burk, R. F., Schaffner, W. & Koenig, M. G. Severe influenza virus pneumonia in the pandemic of 1968–1969. Arch. Intern. Med. 127, 1122–1128 (1971).
Bisno, A. L., Griffin, J. P., Van Epps, K. A., Niell, H. B. & Rytel, M. W. Pneumonia and Hong Kong influenza: a prospective study of the 1968–1969 epidemic. Am. J. Med. Sci. 261, 251–263 (1971).
Sharrar, R. G. National influenza experience in the USA, 1968–1969. Bull World Health Organ. 41, 361–366 (1969).
Gillet, Y. et al. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet 359, 753–759 (2002).
Finelli, L. et al. Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection. Pediatrics 122, 805–811 (2008).
This large epidemiological study shows an increase in influenza virus–S. aureus co-infections with the emergence of the USA300 genotype in the United States.
Iverson, A. R. et al. Influenza virus primes mice for pneumonia from Staphylococcus aureus. J. Infect. Dis. 203, 880–888 (2011).
Watt, J. P. et al. Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates. Lancet 374, 903–911 (2009).
Jennings, L. C. et al. Incidence and characteristics of viral community-acquired pneumonia in adults. Thorax 63, 42–48 (2008).
Chaussee, M. S. et al. Inactivated and live, attenuated influenza vaccines protect mice against influenza: Streptococcus pyogenes super-infections. Vaccine 29, 3773–3781 (2011).
Michelow, I. C. et al. Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children. Pediatrics 113, 701–707 (2004).
Berkley, J. A. et al. Viral etiology of severe pneumonia among Kenyan infants and children. JAMA 303, 2051–2057 (2010).
Olsen, S. J. et al. Incidence of respiratory pathogens in persons hospitalized with pneumonia in two provinces in Thailand. Epidemiol. Infect. 138, 1811–1822 (2010).
Hammitt, L. L. et al. A preliminary study of pneumonia etiology among hospitalized children in Kenya. Clin. Infect. Dis. 54, S190–S199 (2012).
Chen, C. J. et al. Etiology of community-acquired pneumonia in hospitalized children in northern Taiwan. Pediatr. Infect. Dis. J. 31, e196–e201 (2012).
Techasaensiri, B. et al. Viral coinfections in children with invasive pneumococcal disease. Pediatr. Infect. Dis. J. 29, 519–523 (2010).
Peltola, V. et al. Temporal association between rhinovirus circulation in the community and invasive pneumococcal disease in children. Pediatr. Infect. Dis. J. 30, 456–461 (2011).
Dawood, F. S. et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N. Engl. J. Med. 360, 2605–2615 (2009).
Dawood, F. S. et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect. Dis. 12, 687–695 (2012).
Reichert, T., Chowell, G., Nishiura, H., Christensen, R. A. & McCullers, J. A. Does glycosylation as a modifier of Original Antigenic Sin explain the case age distribution and unusual toxicity in pandemic novel H1N1 influenza? BMC Infect. Dis. 10, 5 (2010).
Monsalvo, A. C. et al. Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes. Nature Med. 17, 195–199 (2011).
Charu, V. et al. Mortality burden of the A/H1N1 pandemic in Mexico: a comparison of deaths and years of life lost to seasonal influenza. Clin. Infect. Dis. 53, 985–993 (2011).
Simonsen, L. et al. The impact of influenza epidemics on mortality: introducing a severity index. Am. J. Publ. Health 87, 1944–1950 (1997).
Dominguez-Cherit, G. et al. Critically ill patients with 2009 influenza A (H1N1) in Mexico. JAMA 302, 1880–1887 (2009).
Centers for Disease Control Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) — United States, May–August 2009. Morb. Mortal. Wkly Rep. 58, 1071–1074 (2009).
Mauad, T. et al. Lung pathology in fatal novel human influenza A (H1N1) infection. Am. J. Respir. Crit. Care Med. 181, 72–79 (2010).
Estenssoro, E. et al. Pandemic 2009 influenza A in Argentina: a study of 337 patients on mechanical ventilation. Am. J. Respir. Crit. Care Med. 182, 41–48 (2010).
Shieh, W. J. et al. 2009 pandemic influenza A (H1N1): pathology and pathogenesis of 100 fatal cases in the United States. Am. J. Pathol. 177, 166–175 (2010).
This paper comprehensively describes the pathology of co-infections during the 2009 pandemic.
Rice, T. W. et al. Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States. Crit. Care Med. 40, 1487–1498 (2012).
Nguyen, T. et al. Coinfection with Staphylococcus aureus increases risk of severe coagulopathy in critically ill children with influenza A (H1N1) virus infection. Crit. Care Med. 40, 3246–3250 (2012).
Nelson, J. C. et al. Impact of the introduction of pneumococcal conjugate vaccine on rates of community acquired pneumonia in children and adults. Vaccine 26, 4947–4954 (2008).
Watkins, R. R., David, M. Z. & Salata, R. A. Current concepts on the virulence mechanisms of meticillin-resistant Staphylococcus aureus. J. Med. Microbiol. 61, 1179–1193 (2012).
Ampofo, K. et al. Association of 2009 pandemic influenza A (H1N1) infection and increased hospitalization with parapneumonic empyema in children in Utah. Pediatr. Infect. Dis. J. 29, 905–909 (2010).
Kumar, S. et al. Clinical and epidemiologic characteristics of children hospitalized with 2009 pandemic H1N1 influenza A infection. Pediatr. Infect. Dis. J. 29, 591–594 (2010).
Palacios, G. et al. Streptococcus pneumoniae coinfection is correlated with the severity of H1N1 pandemic influenza. PLoS ONE 4, e8540 (2009).
This paper shows a link between co-infections and more severe outcomes.
Dhanoa, A., Fang, N. C., Hassan, S. S., Kaniappan, P. & Rajasekaram, G. Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection. Virol. J. 8, 501 (2011).
McCullers, J. A. Insights into the interaction between influenza virus and pneumococcus. Clin. Microbiol. Rev. 19, 571–582 (2006).
McCullers, J. A. Preventing and treating secondary bacterial infections with antiviral agents. Antivir. Ther. 16, 123–135 (2011).
This paper reviews the mechanisms and our current knowledge of related treatment modalities for viral–bacterial co-infections.
Loosli, C. G. et al. The destruction of type 2 pneumocytes by airborne influenza PR8-A virus; its effect on surfactant and lecithin content of the pneumonic lesions of mice. Chest 67, 7S–14S (1975).
Johanson, W. G. Jr., Pierce, A. K. & Sanford, J. P. Pulmonary function in uncomplicated influenza. Am. Rev. Respir. Dis. 100, 141–146 (1969).
Horner, G. J. & Gray, F. D. Jr. Effect of uncomplicated, presumptive influenza on the diffusing capacity of the lung. Am. Rev. Respir. Dis. 108, 866–869 (1973).
Levandowski, R. A., Gerrity, T. R. & Garrard, C. S. Modifications of lung clearance mechanisms by acute influenza A infection. J. Lab. Clin. Med. 106, 428–432 (1985).
Glezen, W. P., Greenberg, S. B., Atmar, R. L., Piedra, P. A. & Couch, R. B. Impact of respiratory virus infections on persons with chronic underlying conditions. JAMA 283, 499–505 (2000).
Plotkowski, M. C., Puchelle, E., Beck, G., Jacquot, J. & Hannoun, C. Adherence of type I Streptococcus pneumoniae to tracheal epithelium of mice infected with influenza A/PR8 virus. Am. Rev. Respir. Dis. 134, 1040–1044 (1986).
This paper is a classic study that shows bacterial adherence in areas of virus-mediated epithelial damage.
Plotkowski, M. C., Bajolet-Laudinat, O. & Puchelle, E. Cellular and molecular mechanisms of bacterial adhesion to respiratory mucosa. Eur. Respir. J. 6, 903–916 (1993).
Dockrell, D. H., Whyte, M. K. & Mitchell, T. J. Pneumococcal pneumonia: mechanisms of infection and resolution. Chest 142, 482–491 (2012).
Heilmann, C. Adhesion mechanisms of staphylococci. Adv. Exp. Med. Biol. 715, 105–123 (2011).
Foster, T. J. & Hook, M. Surface protein adhesins of Staphylococcus aureus. Trends Microbiol. 6, 484–488 (1998).
McCullers, J. A. & Tuomanen, E. I. Molecular pathogenesis of pneumococcal pneumonia. Front. Biosci. 6, D877–D889 (2001).
McCullers, J. A. & Rehg, J. E. Lethal synergism between influenza virus and Streptococcus pneumoniae: characterization of a mouse model and the role of platelet-activating factor receptor. J. Infect. Dis. 186, 341–350 (2002).
McAuley, J. L. et al. Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host Microbe 2, 240–249 (2007).
McAuley, J. L. et al. PB1-F2 proteins from H5N1 and 20th century pandemic influenza viruses cause immunopathology. PLoS Pathog. 6, e1001014 (2010).
Alymova, I. V. et al. Immunopathogenic and antibacterial effects of H3N2 influenza A virus PB1-F2 map to amino acid residues 62, 75, 79, and 82. J. Virol. 85, 12324–12333 (2011).
Guarner, J. & Falcon-Escobedo, R. Comparison of the pathology caused by H1N1, H5N1, and H3N2 influenza viruses. Arch. Med. Res. 40, 655–661 (2009).
McCullers, J. A. & Bartmess, K. C. Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. J. Infect. Dis. 187, 1000–1009 (2003).
McCullers, J. A. Effect of antiviral treatment on the outcome of secondary bacterial pneumonia after influenza. J. Infect. Dis. 190, 519–526 (2004).
Camara, M., Mitchell, T. J., Andrew, P. W. & Boulnois, G. J. Streptococcus pneumoniae produces at least two distinct enzymes with neuraminidase activity: cloning and expression of a second neuraminidase gene in Escherichia coli. Infect. Immun. 59, 2856–2858 (1991).
Cundell, D. R. & Tuomanen, E. I. Receptor specificity of adherence of Streptococcus pneumoniae to human type-II pneumocytes and vascular endothelial cells in vitro. Microb. Pathog. 17, 361–374 (1994).
Miller, M. L., Gao, G., Pestina, T., Persons, D. & Tuomanen, E. Hypersusceptibility to invasive pneumococcal infection in experimental sickle cell disease involves platelet-activating factor receptor. J. Infect. Dis. 195, 581–584 (2007).
de Bentzmann, S., Plotkowski, C. & Puchelle, E. Receptors in the Pseudomonas aeruginosa adherence to injured and repairing airway epithelium. Am. J. Respir. Crit. Care Med. 154, S155–S162 (1996).
Martin, P. & Leibovich, S. J. Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol. 15, 599–607 (2005).
Puchelle, E., Zahm, J. M., Tournier, J. M. & Coraux, C. Airway epithelial repair, regeneration, and remodeling after injury in chronic obstructive pulmonary disease. Proc. Am. Thorac. Soc. 3, 726–733 (2006).
Louria, D., Blumenfeld, H., Ellis, J., Kilbourne, E. D. & Rogers, D. Studies on influenza in the pandemic of 1957–1958. II. Pulmonary complications of influenza. J. Clin. Invest. 38, 213–265 (1959).
Webster, R. G., Bean, W. J., Gorman, O. T., Chambers, T. M. & Kawaoka, Y. Evolution and ecology of influenza A viruses. Microbiol. Rev. 56, 152–179 (1992).
Chutinimitkul, S. et al. In vitro assessment of attachment pattern and replication efficiency of H5N1 influenza A viruses with altered receptor specificity. J. Virol. 84, 6825–6833 (2010).
Reading, P. C., Morey, L. S., Crouch, E. C. & Anders, E. M. Collectin-mediated antiviral host defense of the lung: evidence from influenza virus infection of mice. J. Virol. 71, 8204–8212 (1997).
Vigerust, D. J. et al. N-linked glycosylation attenuates H3N2 influenza viruses. J. Virol. 81, 8593–8600 (2007).
Koppe, U., Suttorp, N. & Opitz, B. Recognition of Streptococcus pneumoniae by the innate immune system. Cell. Microbiol. 14, 460–466 (2012).
Joyce, E. A., Popper, S. J. & Falkow, S. Streptococcus pneumoniae nasopharyngeal colonization induces type I interferons and interferon-induced gene expression. BMC Genomics 10, 404 (2009).
Bucasas, K. L. et al. Global gene expression profiling in infants with acute respiratory syncytial virus broncholitis demonstrates systemic activation of interferon signaling networks. Pediatr. Infect. Dis. J. 32, e68–e76 (2013).
Hale, B. G., Randall, R. E., Ortin, J. & Jackson, D. The multifunctional NS1 protein of influenza A viruses. J. Gen. Virol. 89, 2359–2376 (2008).
Kimaro Mlacha, S. Z. et al. Transcriptional adaptation of pneumococci and human pharyngeal cells in the presence of a virus infection. BMC Genomics 14, 378 (2013).
Kukavica-Ibrulj, I. et al. Infection with human metapneumovirus predisposes mice to severe pneumococcal pneumonia. J. Virol. 83, 1341–1349 (2009).
Stark, J. M., Stark, M. A., Colasurdo, G. N. & LeVine, A. M. Decreased bacterial clearance from the lungs of mice following primary respiratory syncytial virus infection. J. Med. Virol. 78, 829–838 (2006).
Alymova, I. V. et al. The novel parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 prevents lethal synergism between a paramyxovirus and Streptococcus pneumoniae. Antimicrob. Agents Chemother. 49, 398–405 (2005).
Sun, K. & Metzger, D. W. Inhibition of pulmonary antibacterial defense by interferon-γ during recovery from influenza infection. Nature Med. 14, 558–564 (2008).
Li, W., Moltedo, B. & Moran, T. M. Type I interferon induction during influenza virus infection increases susceptibility to secondary Streptococcus pneumoniae infection by negative regulation of γδ T cells. J. Virol. 86, 12304–12312 (2012).
Tian, X. et al. Poly I:C enhances susceptibility to secondary pulmonary infections by Gram-positive bacteria. PLoS ONE 7, e41879 (2012).
Shahangian, A. et al. Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice. J. Clin. Invest. 119, 1910–1920 (2009).
Koppe, U. et al. Streptococcus pneumoniae stimulates a STING- and IFN regulatory factor 3-dependent type I IFN production in macrophages, which regulates RANTES production in macrophages, cocultured alveolar epithelial cells, and mouse lungs. J. Immunol. 188, 811–817 (2012).
Parker, D. et al. Streptococcus pneumoniae DNA initiates type I interferon signaling in the respiratory tract. mBio 2, e00016–00011 (2011).
Small, C. L. et al. Influenza infection leads to increased susceptibility to subsequent bacterial superinfection by impairing NK cell responses in the lung. J. Immunol. 184, 2048–2056 (2010).
Ghoneim, H. E., Thomas, P. G. & McCullers, J. A. Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections. J. Immunol. 191, 1250–1259 (2013).
Snelgrove, R. J. et al. A critical function for CD200 in lung immune homeostasis and the severity of influenza infection. Nature Immunol. 9, 1074–1083 (2008).
Hussell, T. & Cavanagh, M. M. The innate immune rheostat: influence on lung inflammatory disease and secondary bacterial pneumonia. Biochem. Soc. Trans. 37, 811–813 (2009).
van der Sluijs, K. F. et al. IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection. J. Immunol. 172, 7603–7609 (2004).
Metzger, D. W. & Sun, K. Immune dysfunction and bacterial coinfections following influenza. J. Immunol. 191, 2047–2052 (2013).
Goulding, J. et al. Lowering the threshold of lung innate immune cell activation alters susceptibility to secondary bacterial superinfection. J. Infect. Dis. 204, 1086–1094 (2011).
Didierlaurent, A. et al. Sustained desensitization to bacterial Toll-like receptor ligands after resolution of respiratory influenza infection. J. Exp. Med. 205, 323–329 (2008).
This paper shows that innate immune defects persist for months after influenza in mice.
Ludewick, H. P., Aerts, L., Hamelin, M. E. & Boivin, G. Long-term impairment of Streptococcus pneumoniae lung clearance is observed after initial infection with influenza A virus but not human metapneumovirus in mice. J. Gen. Virol. 92, 1662–1665 (2011).
Chen, W. et al. A novel influenza A virus mitochondrial protein that induces cell death. Nature Med. 7, 1306–1312 (2001).
Conenello, G. M., Zamarin, D., Perrone, L. A., Tumpey, T. & Palese, P. A single mutation in the PB1-F2 of H5N1 (HK/97) and 1918 influenza A viruses contributes to increased virulence. PLoS Pathog. 3, 1414–1421 (2007).
Weeks-Gorospe, J. N. et al. Naturally occurring swine influenza A virus PB1-F2 phenotypes that contribute to superinfection with Gram-positive respiratory pathogens. J. Virol. 86, 9035–9043 (2012).
Tuomanen, E. I., Austrian, R. & Masure, H. R. Pathogenesis of pneumococcal infection. N. Engl. J. Med. 332, 1280–1284 (1995).
Rogolsky, M. Nonenteric toxins of Staphylococcus aureus. Microbiol. Rev. 43, 320–360 (1979).
Boulnois, G. J., Paton, J. C., Mitchell, T. J. & Andrew, P. W. Structure and function of pneumolysin, the multifunctional, thiol-activated toxin of Streptococcus pneumoniae. Mol. Microbiol. 5, 2611–2616 (1991).
Ramos, I. & Fernandez-Sesma, A. Cell receptors for influenza A viruses and the innate immune response. Front. Microbiol. 3, 117 (2012).
Kuri, T. et al. Influenza A virus-mediated priming enhances cytokine secretion by human dendritic cells infected with Streptococcus pneumoniae. Cell. Microbiol. 15, 1385–1400 (2013).
Imai, Y. et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 133, 235–249 (2008).
Klein, K. P., Tan, L., Werkman, W., van Bleek, G. M. & Coenjaerts, F. The role of Toll-like receptors in regulating the immune response against respiratory syncytial virus. Crit. Rev. Immunol. 29, 531–550 (2009).
Karlstrom, A., Heston, S. M., Boyd, K. L., Tuomanen, E. I. & McCullers, J. A. Toll-like receptor 2 mediates fatal immunopathology in mice during treatment of secondary pneumococcal pneumonia following influenza. J. Infect. Dis. 204, 1358–1366 (2011).
Weiss, S. J. Tissue destruction by neutrophils. N. Engl. J. Med. 320, 365–376 (1989).
Kash, J. C. et al. Lethal synergism of 2009 pandemic H1N1 influenza virus and Streptococcus pneumoniae coinfection is associated with loss of murine lung repair responses. mBio 2, e00172 (2011).
Wang, J. et al. Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages. Nature Commun. 4, 2106 (2013).
Tashiro, M., Ciborowski, P., Klenk, H. D., Pulverer, G. & Rott, R. Role of Staphylococcus protease in the development of influenza pneumonia. Nature 325, 536–537 (1987).
Ichinohe, T. et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc. Natl Acad. Sci. USA 108, 5354–5359 (2011).
Abt, M. C. et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity 37, 158–170 (2012).
Kasowski, E. J., Garten, R. J. & Bridges, C. B. Influenza pandemic epidemiologic and virologic diversity: reminding ourselves of the possibilities. Clin. Infect. Dis. 52, S44–S49 (2011).
Klugman, K. P., Chien, Y. W. & Madhi, S. A. Pneumococcal pneumonia and influenza: a deadly combination. Vaccine 27, C9–C14 (2009).
Mediavilla, J. R., Chen, L., Mathema, B. & Kreiswirth, B. N. Global epidemiology of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA). Curr. Opin. Microbiol. 15, 588–595 (2012).
Peebles, P. J., Dhara, R., Brammer, L., Fry, A. M. & Finelli, L. Influenza-associated mortality among children — United States: 2007–2008. Influenza Other Respir. Viruses 5, 25–31 (2011).
McCullers, J. A. et al. Influenza enhances susceptibility to natural acquisition of and disease due to Streptococcus pneumoniae in ferrets. J. Infect. Dis. 202, 1287–1295 (2010).
Fleming-Dutra, K. E. et al. Effect of the 2009 influenza A (H1N1) pandemic on invasive pneumococcal pneumonia. J. Infect. Dis. 207, 1135–1143 (2013).
This paper presents the first large study associating specific pneumococcal serotypes with influenza.
Wong, S. M., Bernui, M., Shen, H. & Akerley, B. J. Genome-wide fitness profiling reveals adaptations required by Haemophilus in coinfection with influenza A virus in the murine lung. Proc. Natl Acad. Sci. USA 110, 15413–15418 (2013).
Morens, D. M. & Taubenberger, J. K. Pandemic influenza: certain uncertainties. Rev. Med. Virol. 21, 262–284 (2011).
Laennec, R. T. H. in Translation of Selected Passages from De l'Auscultation Mediate 88–95 (Williams Wood & Co., 1923).
Wherry, W. B. & Butterfield, C. T. Inhalation experiments on influenza and pneumonia, and on the importance of spray-borne bacteria in respiratory infections. J. Infect. Dis. 27, 315–326 (1920).
Shope, R. E. Swine influenza. I. Experimental transmission and pathology. II. A hemophilic bacillus from the respiratory tract of infected swine. III. Filtration experiments and etiology. J. Exp. Med. 54, 349–385 (1931).
This is a classic paper showing that the manifestation of disease during viral infection requires a co-infecting pathogen.
Francis, T. E. & de Torregrosa, M. V. Combined infection of mice with H. influenzae and influenza virus by the intranasal route. J. Infect. Dis. 76, 70–77 (1945).
Avadhanula, V. et al. Respiratory viruses augment the adhesion of bacterial pathogens to respiratory epithelium in a viral species- and cell type-dependent manner. J. Virol. 80, 1629–1636 (2006).
Vissers, M. et al. Respiratory syncytial virus infection augments NOD2 signaling in an IFN-β-dependent manner in human primary cells. Eur. J. Immunol. 42, 2727–2735 (2012).
Ren, J. et al. Human metapneumovirus inhibits IFN-β signaling by downregulating Jak1 and Tyk2 cellular levels. PLoS ONE 6, e24496 (2011).
Radin, J. N. et al. β-Arrestin 1 participates in platelet-activating factor receptor-mediated endocytosis of Streptococcus pneumoniae. Infect. Immun. 73, 7827–7835 (2005).
Vernatter, J. & Pirofski, L. A. Current concepts in host–microbe interaction leading to pneumococcal pneumonia. Curr. Opin. Infect. Dis. 26, 277–283 (2013).
Marks, L. R., Davidson, B. A., Knight, P. R. & Hakansson, A. P. Interkingdom signaling induces Streptococcus pneumoniae biofilm dispersion and transition from asymptomatic colonization to disease. mBio 4, e00438 (2013).
Shrestha, S. et al. Identifying the interaction between influenza and pneumococcal pneumonia using incidence data. Sci. Transl. Med. 5, 191ra84 (2013).
Smith, A. M. et al. Kinetics of coinfection with influenza A virus and Streptococcus pneumoniae. PLoS Pathog. 9, e1003238 (2013).
Peltola, V. T., Murti, K. G. & McCullers, J. A. Influenza virus neuraminidase contributes to secondary bacterial pneumonia. J. Infect. Dis. 192, 249–257 (2005).