Norberto Gonzalez-Juarbe (United States of America)
J. Craig Venter Institute
Infectious Diseases and Genomic Medicine
Norberto Gonzalez-Juarbe is an assistant professor working in the Infectious Diseases and Genomic Medicine Group. Currently, he is focused on the host responses that occur during co- and secondary bacterial infections to influenza. Dr. Gonzalez-Juarbe began his science career researching the habitability of primary producers in the field of astrobiology. Later while working on his PhD, his research was one of the first to establish that bacterial pathogens use pore-forming toxins to deplete the lungs of alveolar macrophages through activation of necroptosis (programmed necrosis). As a postdoctoral fellow at the University of Alabama in Birmingham, under the supervision of Dr. Carlos Orihuela, Dr. Gonzalez-Juarbe focused on the study of Streptococcus pneumoniae-induced cardiac damage during invasive pneumococcal disease and expanded his graduate work on how bacterial pore-forming toxins cause cell death and the immunological implications of these mechanisms.

Presenter of 1 Presentation

 Conference Calendar

O070 - EXTRAPULMONARY SYNERGISM: INFLUENZA PROMOTES STREPTOCOCCUS PNEUMONIAE CARDIAC PATHOGENESIS (ID 823)

Session Name
0730 - Parallel Session 12: Late-Breaking Quick Hits (ID 68)
Session Type
Parallel Session
Date
Wed, 22.06.2022
Session Time
15:05 - 16:50
Room
Grand Ballroom Centre
Presenter
Lecture Time
16:19 - 16:27

Abstract

Background

It has been extensively reported that primary influenza infection promotes the development of a lethal form of Streptococcus pneumoniae (Spn) pulmonary disease. Recently, pneumonia events caused by both viruses and bacteria have been directly associated with cardiac damage. It is not known whether viral-bacterial synergy extends to extrapulmonary organs such as the heart.

Methods

Here we used a mouse model of secondary infection (SI) were mice are infected with pandemic influenza A virus (IAV) and then challenged with Spn. Using label-free quantitative proteomics we assessed the effects of SI to cardiac biology. We determined cardiac bacterial titers, and used immunoblots and isogenic deletion bacterial mutants to validate proteomic observations. We used mice deficient in necroptosis to discern the requirement of this pathway in vitro and in vivo.

Results

We report that primary infection with pandemic IAV leads to increased Spn translocation to the myocardium. We also observed that each infection alone led to proteomic changes in the heart, and these were exacerbated in the SI model. Gene ontology analysis of significantly upregulated proteins showed increased innate immune activity, oxidative processes, and changes to ion homeostasis during SI. Immunoblots confirmed increase complement, antioxidants and ACE2. Using an in vitro model of SI, we observed that influenza enhances Spn cell cytotoxicity and bacterial adhesion to cardiomyocytes. Mice deficient in necroptosis showed enhanced innate immune responses and mitochondrial function, and decreased virus-associated pathways.

Conclusions

The presented results provide the first in vivo evidence that influenza infection promotes Spn infiltration, necrotic damage, and proteomic remodeling of the heart.

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