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. 2022 Nov 19;9(12):ofac629.
doi: 10.1093/ofid/ofac629. eCollection 2022 Dec.

Pro-Inflammatory Alterations of Circulating Monocytes in Latent Tuberculosis Infection

Manuel G Feria  1 , Cecilia Chang  2 , Eduardo Ticona  3   4 , Anissa Moussa  1 , Bin Zhang  5   6 , Isabel Ballena  3 , Ruben Azañero  3 , Cesar Ticona  3 , Carlo N De Cecco  7 , Carl J Fichtenbaum  1 , Robert E O'Donnell  8 , Alberto La Rosa  2 , Jorge Sanchez  2   9 , Sandra Andorf  5   6   10 , Laura Atehortua  11   12 , Jonathan D Katz  6   11   12 , Claire A Chougnet  6   11   12 , George S Deepe Jr  1   12 , Moises A Huaman  1   12
Affiliations

Pro-Inflammatory Alterations of Circulating Monocytes in Latent Tuberculosis Infection

Manuel G Feria et al. Open Forum Infect Dis. .

Abstract

Background: Latent tuberculosis infection (LTBI) has been associated with increased cardiovascular risk. We investigated the activation and pro-inflammatory profile of monocytes in individuals with LTBI and their association with coronary artery disease (CAD).

Methods: Individuals 40-70 years old in Lima, Peru, underwent QuantiFERON-TB testing to define LTBI, completed a coronary computed tomography angiography to evaluate CAD, and provided blood for monocyte profiling using flow cytometry. Cells were stimulated with lipopolysaccharide to assess interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α responses.

Results: The clinical characteristics of the LTBI (n = 28) and non-LTBI (n = 41) groups were similar. All monocyte subsets from LTBI individuals exhibited higher mean fluorescence intensity (MFI) of CX3CR1 and CD36 compared with non-LTBI individuals. LTBI individuals had an increased proportion of nonclassical monocytes expressing IL-6 (44.9 vs 26.9; P = .014), TNF-α (62.3 vs 35.1; P = .014), and TNF-α+IL-6+ (43.2 vs 36.6; P = .042). Among LTBI individuals, CAD was associated with lower CX3CR1 MFI on classical monocytes and lower CD36 MFI across all monocyte subsets. In multivariable analyses, lower CD36 MFI on total monocytes (b = -0.17; P = .002) and all subsets remained independently associated with CAD in LTBI.

Conclusions: Individuals with LTBI have distinct monocyte alterations suggestive of an exacerbated inflammatory response and tissue migration. Whether these alterations contribute to cardiovascular disease pathogenesis warrants further investigation.

Keywords: cardiovascular disease; coronary artery disease; inflammation; latent tuberculosis; monocytes.

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Conflict of interest statement

Potential conflicts of interest. C. J. F. reports grants from Gilead Sciences, Inc., grants from ViiV Healthcare, Janssen, Amgen, Merck, and Cytodyn, and personal fees from Clinical Care Options, outside the submitted work. M.A.H. reports contracts from Gilead Sciences, Inc., and Insmed, Inc., to the University of Cincinnati, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Immunophenotyping of monocytes in LTBI. A, Percentage of total monocytes, classical monocytes, intermediate monocytes, and nonclassical monocytes in non-LTBI and LTBI individuals. MFI of (B) CX3XR1 and (C) CD36 on total monocytes, classical monocytes, intermediate monocytes, and nonclassical monocytes in the non-LTBI and LTBI groups. P values are from the Mann-Whitney test. P values <.05 are considered significant. Abbreviations: LTBI, latent tuberculosis infection; MRI, mean fluorescence intensity; ns, not statistically significant.
Figure 2.
Figure 2.
Alteration in the proinflammatory response of LPS-stimulated monocytes from LTBI individuals. Peripheral blood mononuclear cells were stimulated with LPS 1 μg/mL for 6 hours. Unstimulated control was included. A, Gating strategy for detection of nonclassical monocytes (CD14dimCD16+) positive for IL-6, TNF-α, and IL-6+ TNF-α+. Percentage of nonclassical monocytes positive for (B) IL-6, (C) TNF-α+, and (D) IL-6+ TNF-α+ from the non-LTBI (green color) and LTBI (red color) groups. P values are from the Mann-Whitney test. P values <.05 are considered significant. Abbreviations: IL-6, interleukin-6; LTBI, latent tuberculosis infection; LPS, lipopolysaccharide; ns, not statistically significant; TNF, tumor necrosis factor.
Figure 3.
Figure 3.
Immune alteration in monocytes from LTBI and their association with CAD. Baseline MFI of (A) CX3CR1 and (B) CD36 on total monocytes, classical monocytes, intermedial monocytes, and nonclassical monocytes in non-CAD (yellow color) and CAD (yellow color) individuals with non-LTBI or LTBI. P values are from the Mann-Whitney test. P values <.05 are considered significant. Abbreviations: CAD, coronary artery disease; LTBI, latent tuberculosis infection; MFI, mean fluorescence intensity; ns, not statistically significant.
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