Immune activation during Paenibacillus brain infection in African infants with frequent cytomegalovirus co-infection

Albert M. Isaacs, Sarah U. Morton, Mercedeh Movassagh, Qiang Zhang, Christine Hehnly, Lijun Zhang, Diego M. Morales, Shamim A. Sinnar, Jessica E. Ericson, Edith Mbabazi-Kabachelor, Peter Ssenyonga, Justin Onen, Ronnie Mulondo, Mady Hornig, Benjamin C. Warf, James R. Broach, R. Reid Townsend, David D. Limbrick, Joseph N. Paulson, Steven J. Schiff

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammation during neonatal brain infections leads to significant secondary sequelae such as hydrocephalus, which often follows neonatal sepsis in the developing world. In 100 African hydrocephalic infants we identified the biological pathways that account for this response. The dominant bacterial pathogen was a Paenibacillus species, with frequent cytomegalovirus co-infection. A proteogenomic strategy was employed to confirm host immune response to Paenibacillus and to define the interplay within the host immune response network. Immune activation emphasized neuroinflammation, oxidative stress reaction, and extracellular matrix organization. The innate immune system response included neutrophil activity, signaling via IL-4, IL-12, IL-13, interferon, and Jak/STAT pathways. Platelet-activating factors and factors involved with microbe recognition such as Class I MHC antigen-presenting complex were also increased. Evidence suggests that dysregulated neuroinflammation propagates inflammatory hydrocephalus, and these pathways are potential targets for adjunctive treatments to reduce the hazards of neuroinflammation and risk of hydrocephalus following neonatal sepsis.

Original languageEnglish (US)
Article number102351
JournaliScience
Volume24
Issue number4
DOIs
StatePublished - Apr 23 2021

All Science Journal Classification (ASJC) codes

  • General

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