Dual RNA Sequencing of -Infected Human Splenic Macrophages Reveals a Strain-Dependent Host-Pathogen Response to Infection

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Feb 15

PMID 35163725

Authors

Victor A Lopez-Agudelo

Andres Baena

Vianey Barrera

Felipe Cabarcas

Juan F Alzate

Dany J V Beste

Rigoberto Rios-Estepa

Luis F Barrera

Affiliations

Soon will be listed here.

Abstract

Tuberculosis (TB) is caused by (Mtb), leading to pulmonary and extrapulmonary TB, whereby Mtb is disseminated to many other organs and tissues. Dissemination occurs early during the disease, and bacteria can be found first in the lymph nodes adjacent to the lungs and then later in the extrapulmonary organs, including the spleen. The early global gene expression response of human tissue macrophages and intracellular clinical isolates of Mtb has been poorly studied. Using dual RNA-seq, we have explored the mRNA profiles of two closely related clinical strains of the Latin American and Mediterranean (LAM) family of Mtb in infected human splenic macrophages (hSMs). This work shows that these pathogens mediate a distinct host response despite their genetic similarity. Using a genome-scale host-pathogen metabolic reconstruction to analyze the data further, we highlight that the infecting Mtb strain also determines the metabolic response of both the host and pathogen. Thus, macrophage ontogeny and the genetic-derived program of Mtb direct the host-pathogen interaction.

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