Gastrointestinal Helminths Increase Bordetella bronchiseptica Shedding and Host Variation in Supershedding

Abstract

Multi-species infections have been suggested to facilitate pathogen transmission and the emergence of supershedding events. However, how the interactions between co-infecting pathogens affect their dynamics of shedding, and how this is related to the host immune response, remains largely unclear. We used laboratory experiments and a modeling approach to examine temporal variations in the shedding of the respiratory bacterium Bordetella bronchiseptica in rabbits challenged with one or two gastrointestinal helminth species. Experimental data showed that rabbits co-infected with one or both helminths shed significantly more B. bronchiseptica by direct contact with an agar petri dish than rabbits with bacteria alone. There was also evidence of synergistic effects when both helminth species were present (triple infection). Co-infected hosts generated supershedding events of higher intensity and more frequently than hosts with no helminths. Model simulations revealed that the two helminths affected the relative contribution of neutrophils and specific IgA and IgG to B. bronchiseptica neutralization in the respiratory tract. In turn, these changes led to differences in the magnitude and duration of shedding among the various types of infection. However, the rapid variation in individual shedding, including supershedding, could not be explained by the interactions between infection and immune response at the scale of analysis that we used. We suggest that local rapid changes at the level of respiratory tissue probably played a more important role. This study provides novel insight into the role of helminths to the dynamics of respiratory infections and offers a quantitative explanation for the differences generated by two helminth species. Author summaryThe dynamics of bacterial infections can be facilitated by the presence of gastrointestinal helminths. Understanding the immunological processes that underline the pathogen-parasite interactions, and how they affect the dynamics of shedding, is important particularly for infections where control of the parasite maybe more effective than trying to reduce the bacterial infection. In this study, we examined the role of two gastrointestinal helminth species on the shedding of the respiratory Bordetella bronchiseptica using laboratory experiments of rabbits together with mathematical modeling. Hosts infected with helminths shed significantly more bacteria with evidence of supershedding, than hosts with only B. bronchiseptica. Simulations showed that by altering the relative contribution of neutrophils, specific IgA and IgG, helminths affected the control of bacterial infection in the respiratory tract. These interactions altered the intensity and duration of bacterial shedding, including the frequency and intensity of supershedding events. However, at the host level our model did not explain the rapid variation in shedding observed, suggesting that local processes in the respiratory tissue are critical for the prediction of the daily shed in the environment. This study advances our understanding of the dynamics of shedding in bacteria-helminth co-infections and provides insight that can be used to control disease spread.