CI DYNAMICS

Growth and Density

 * Study utilizing a mouse model of otitis media, CI with IAV resulted in an increase in bacterial growth and middle ear inflammation compared to SP infection alone, implicating viral inflammation in bacterial growth (VERNATTER; PIROFSKI, 2013).
 * Total bacteria numbers recovered from IV-infected mice were significantly greater compared to mice without IV infection (KING; LEI; HARMSEN, 2009).
 * When compared to mice infected with IV alone, mice co-infected with IV followed by SP had significant body weight loss and 100% mortality (WU et al., 2015).
 * Increased density of colonizing bacteria on mice with CI (NAKAMURA; DAVIS; WEISER, 2011).
 * 1000-fold higher bacterial counts at 48 h after infection with SP (VAN DER SLUIJS et al., 2004).
 * In contrast to SP-infection alone, co-infected animals were unable to control the exponential growth of SP (STEGEMANN et al., 2009).
 * CI elevated the bacterial load compared to animals infected with bacteria alone (MOORTHY et al., 2013).
 * IV causes a long-term modification of the lung micro-environment by a desensitization to bacterial products and an increase in the myeloid negative regulator CD200R (CD200 receptor). These two events prevent subsequent inflammatory damage while the lung is healing, but also they may predispose to bacterial colonization of the lower respiratory tract should regulatory mechanisms overshoot (HUSSELL; CAVANAGH, 2009).
 * IV accelerates bacterial replication in vivo (SIEGEL; ROCHE; WEISER, 2014).
 * In the lung, lethal CI significantly increased virus titer and bacterial cell counts (WU et al., 2015).

Carriage and Transmission

 * Innate immune response to IV promotes bacterial shedding, allowing the bacteria to transit from host to host (RICHARD et al., 2014).
 * In the context of CI with IAV, the SP was transmitted among WT littermates, with approximately half of the contact mice acquiring colonization (RICHARD et al., 2014).
 * Mice deficient for TLR2 were colonized to a similar density but transmitted SP more efficiently (100% transmission) (RICHARD et al., 2014).
 * The greater viral burden in TLR2 KO mice correlated with heightened inflammation, and was responsible for an increase in bacterial shedding from the mouse nose (RICHARD et al., 2014).
 * Infant mice were colonized with SP and subsequently infected with IAV which increased SP colonization (DIAVATOPOULOS et al., 2010).
 * In vivo imaging showed that IAV was essential for the transmission of SP from colonized mice to their naive cohoused littermates. Transmission occurred only when all mice were infected with IAV and was prevented when an IAV-neutralizing Ab was used to inhibit IAV replication in either mice (DIAVATOPOULOS et al., 2010).
 * Increasing the nasopharyngeal load of SP in the colonized index mice (via the depletion of neutrophils) facilitates SP transmission (SHORT et al., 2012).
 * Inducing a proinflammatory response in the naive co-housed contact mice (as demonstrated by cytokine production) facilitates the spread of SP (SHORT et al., 2012).
 * Mice infected with IV for 6 days, but not 3 days, showed a significant increase in susceptibility to SP infection compared to mice not infected with IV (MCNAMEE; HARMSEN, 2006).

Invasive Disease

 * Mice recovered from IV infection were highly susceptible to subsequent SP pneumonia, as reflected by a 100% lethality on day 3 after bacterial infection, whereas control mice showed 17% lethality on day 3 and 83% lethality on day 6 after SP infection (VAN DER SLUIJS et al., 2004).
 * CI augments susceptibility to invasive infection (NAKAMURA; DAVIS; WEISER, 2011).
 * Infant mice were colonized with SP and subsequently infected with IAV showed increased invasive disease (DIAVATOPOULOS et al., 2010).
 * IV infection preceding SP challenge primed for pneumonia and led to 100% mortality (MCCULLERS; REHG, 2002).
 * Sequential SP infection of mice previously inoculated with isogenic recombinant H2N2and H9N2 IV displayed severe pneumonia, elevated levels of intrapulmonary proinflammatory responses, and death (CHOCKALINGAM et al., 2012).
 * Enhanced lung pathogenesis was observed in CI mice compared to those challenged with IV or bacteria alone (MOORTHY et al., 2013).
 * PR8-recovered mice (mice adapted for IV infection) developed a rapidly fatal pulmonary infection to a 100-fold sublethal SP challenge, whereas PR8-naive mice demonstrated no mortality or illness (CHEN et al., 2012).
 * CI animals experienced rapid weight loss and succumbed to infection (DAMJANOVIC et al., 2013).