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

• Published in: International journal of molecular sciences Vol. 23; no. 3; p. 1803
• Main Authors: López-Agudelo, Víctor A, Baena, Andres, Barrera, Vianey, Cabarcas, Felipe, Alzate, Juan F, Beste, Dany J V, Ríos-Estepa, Rigoberto, Barrera, Luis F
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04-02-2022; MDPI
• Subjects: Apoptosis; Cell cycle; Clinical isolates; clinical strains; dual RNA-seq; Fatty acids; Gene expression; Genomes; Host-Pathogen Interactions - genetics; human; Human tissues; Humans; Infections; Lymph nodes; Macrophages; Macrophages - metabolism; metabolic reconstruction; Metabolic response; Metabolism; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Ontogeny; Organs; Pathogens; RNA-Seq; Spleen; splenic macrophages; Tuberculosis; Tuberculosis - microbiology; metabolic reconstruction; Mycobacterium tuberculosis; human; clinical strains; dual RNA-seq; splenic macrophages
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23031803

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.