Pathogen Replication, Host Inflammation, and Disease in the Upper Respiratory Tract

Influenza virus and respiratory bacterial synergy, a term oftenused when describing the relationship between these two highly divergent phyla of respiratory tract pathogens, has been known and documented for nearly a century (1–3). The first conclusive reports date back to 1931, when a young scientist, Richard Shope, and his mentor, Paul Lewis, demonstrated that, by infecting pigs initially with an influenza virus and then withHaemophilus influ-enzae, they could induce disease more severe than that seen with either of the two pathogens in isolation (3, 4). These experiments clarified at least in part the seemingly contradictory findings of Richard Pfeiffer with his discovery in 1892 ofH. influenzae, which he believed was the causative agent of influenza (5), and of Olitsky and Gates, who postulated in 1921 that the causative agent of influenza was indeed a virus (6). In hindsight, Pfeiffer was proba-bly more correct than he was given credit for, with his finding that a bacterial pathogen was associated with the severe disease often