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Jenna Reed, Douglas Cornwall, Nathan Jacobs, Brian D Evavold, Tracey J Lamb, Plasmodium infection elevates risk of severe secondary bacterial disease by altering the immunological landscape of the lung, The Journal of Immunology, Volume 208, Issue Supplement_1, May 2022, Page 170.30, https://doi.org/10.4049/jimmunol.208.Supp.170.30
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Abstract
Lower respiratory infections cause an estimated two million sepsis deaths yearly, with >50% attributed to the opportunistic pathogen Streptococcus pneumoniae. Sub-Saharan Africa, the site of most severe Streptococcus burden, is also ravaged by the malaria-causing Plasmodium parasite family, which afflicted 241 million people and killed 627,000 in 2020. Compared to healthy children, those with asymptomatic malaria have an elevated risk to severe bacterial infections, but the underlying mechanism(s) remain elusive. To fill this knowledge gap, we infected C57BL/6J mice with P. berghei NK65-NY either 7, 14, or 21 days prior to inoculation with S. pneumoniae 6304. Coinfected mice exhibited a 40–60% fatality rate, with death beginning 1–4 days post-bacterial infection. In contrast, singly infected groups survived the duration of the experiment. Coinfected mice exhibited equivalent parasitemia but significantly higher bacterial burden in the lung compared to mono-infections. Neutrophil recruitment and ROS production was altered in coinfected mice, which we predict is due to the formerly described effects of the Plasmodium metabolic product hemozoin. As such, we hypothesize that neutrophil control of S. pneumoniae is impaired. Since malaria has been shown to increase blood brain barrier permeability, we used Evans blue dye to test for a similar effect at the alveolar-capillary interface. Lung weight significantly increased as early as 6 days post-infection, while permeability trended towards a slight increase, peaking at day 9. Thus, we hypothesize that Plasmodium infection increases pathogenicity of Streptococcus infection due to a combination of impaired bacterial control and increased vascular leak in the lungs.
This work was supported by the NIH (ROl AI123425-01A1).
