Human Alveolar and Splenic Macrophage Populations Display a Distinct Transcriptomic Response to Infection With Mycobacterium tuberculosis.

Lelia Lavalett,Hector Ortega,Luis F Barrera

doi:10.3389/fimmu.2020.00630

Lelia Lavalett, Hector Ortega + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2020.00630

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Abstract

Mycobacterium tuberculosis (Mtb) infects alveolar macrophages (AMs), causing pulmonary tuberculosis (PTB), the most common form of the disease. Less frequently, Mtb is disseminated to many other organs and tissues, resulting in different extrapulmonary forms of TB. Nevertheless, very few studies have addressed the global mRNA response of human AMs, particularly from humans with the active form of the disease. Strikingly, almost no studies have addressed the response of human extrapulmonary macrophages to Mtb infection. In this pilot study, using microarray technology, we examined the transcriptomic ex vivo response of AMs from PTB patients (AMTBs) and AMs from control subjects (AMCTs) infected with two clinical isolates of Mtb. Furthermore, we also studied the infection response of human splenic macrophages (SMs) to Mtb isolates, as a model for extrapulmonary infection, and compared the transcriptomic response between AMs and SMs. Our results showed a striking difference in global mRNA profiles in response to infection between AMs and SMs, implicating a tissue-specific macrophage response to Mtb.

Highlights

Different cell populations of the mononuclear phagocytic system (MPS), including macrophages and monocytes, are preferred targets of Mycobacterium tuberculosis (Mtb), the agent causing human tuberculosis (TB)
This grouping was not discriminated between the infection with the clinical isolates UT127 and UT205, suggesting a lower response to Mtb infection compared to alveolar macrophages (AMs)
Compared to alveolar macrophages from control subjects (AMCT), infection of alveolar macrophages from tuberculosis patients (AMTB) with Mtb induced the expression of interferon-stimulated genes (ISG), by upregulating interferon-induced proteins with tetratricopeptide repeats (IFIT) family genes and guanylate-binding proteins (GBP)

Summary

Introduction

Different cell populations of the mononuclear phagocytic system (MPS), including macrophages and monocytes, are preferred targets of Mycobacterium tuberculosis (Mtb), the agent causing human tuberculosis (TB). Of interest is the observation that 1.7 billion people are suspected to be latently infected with Mtb and are at higher risk of developing the active form of the disease [2]. The bacillus is transported to the lung alveoli, Human Macrophages Response to Mtb where alveolar macrophages (AMs) are considered the main targets of the initial infection [3]. In some circumstances, Mtb can be disseminated to other organs and tissues, causing different extrapulmonary TB forms of the disease [4]

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