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. 2023 Mar 27:16:1357-1373.
doi: 10.2147/JIR.S394608. eCollection 2023.

Metabolomic Profiling of Lungs from Mice Reveals the Variability of Metabolites in Pneumocystis Infection and the Metabolic Abnormalities in BAFF-R-Deficient Mice

Heng-Mo Rong #  1 , Han-Yu-Jie Kang #  1 , Zhao-Hui Tong  1
Affiliations

Metabolomic Profiling of Lungs from Mice Reveals the Variability of Metabolites in Pneumocystis Infection and the Metabolic Abnormalities in BAFF-R-Deficient Mice

Heng-Mo Rong et al. J Inflamm Res. .

Abstract

Purpose: The incidence of Pneumocystis pneumonia (PCP) in patients without human immunodeficiency virus (HIV) has been increasing. In this study, we aimed to investigate the metabolic changes in Pneumocystis infection and the metabolic abnormalities in B-cell-activating factor receptor (BAFF-R)-deficient mice with Pneumocystis infection.

Methods: The important function of B cells during Pneumocystis infection is increasingly recognized. In this study, a Pneumocystis-infected mouse model was constructed in BAFF-R-/- mice and wild-type (WT) mice. Lungs of uninfected WT C57BL/6, WT Pneumocystis-infected, and BAFF-R-/- Pneumocystis-infected mice were used for metabolomic analyses to compare the metabolomic profiles among the groups, with the aim of exploring the metabolic influence of Pneumocystis infection and the influence of mature B-cell deficiency during infection.

Results: The results indicated that many metabolites, mainly lipids and lipid-like molecules, were dysregulated in Pneumocystis-infected WT mice compared with uninfected WT C57BL/6 mice. The data also demonstrated significant changes in tryptophan metabolism, and the expression levels of key enzymes of tryptophan metabolism, such as indoleamine 2,3-dioxygenase 1 (IDO1), were significantly upregulated. In addition, B-cell development and function might be associated with lipid metabolism. We found a lower level of alitretinoin and the abnormalities of fatty acid metabolism in BAFF-R-/- Pneumocystis-infected mice. The mRNA levels of enzymes associated with fatty acid metabolism in the lung were upregulated in BAFF-R-/- Pneumocystis-infected mice and positively correlated with the level of IL17A, thus suggesting that the abnormalities of fatty acid metabolism may be associated with greater inflammatory cell infiltration in the lung tissue of BAFF-R-/- Pneumocystis-infected mice compared with the WT Pneumocystis-infected mice.

Conclusion: Our data revealed the variability of metabolites in Pneumocystis-infected mice, suggesting that the metabolism plays a vital role in the immune response to Pneumocystis infection.

Keywords: B lymphocytes; Pneumocystis pneumonia; inflammation; metabolomics.

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Conflict of interest statement

These authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Scatter plot of scores based on the PCA model. (A) Positive ion (ESI+) scan between the control group and Pneumocystis-infected wild-type (WT) mice; (B) Negative ion (ESI−) scan between the control group and Pneumocystis-infected WT mice; (C) ESI+ scan between the Pneumocystis-infected WT mice and Pneumocystis-infected BAFF-R–/– mice; (D) ESI− scan between the Pneumocystis-infected WT mice and Pneumocystis-infected BAFF-R–/– mice.
Figure 2
Figure 2
Scatter plot of scores based on the OPLS-DA model. (A) ESI+ scan between the control group and Pneumocystis-infected WT mice; (B) ESI− scan between the control group and Pneumocystis-infected WT mice; (C) ESI+ scan between the Pneumocystis-infected WT mice and Pneumocystis-infected BAFF-R–/– mice; (D) ESI− scan between the Pneumocystis-infected WT mice and Pneumocystis-infected BAFF-R–/– mice.
Figure 3
Figure 3
Volcano plot showing the number and distribution of lung metabolites in the control group and Pneumocystis-infected WT mice. (A) Positive and (B) negative ion modes.
Figure 4
Figure 4
Volcano plot showing the number and distribution of lung metabolites in the Pneumocystis-infected WT mice and Pneumocystis-infected BAFF-R–/– mice. (A) Positive and (B) negative ion modes.
Figure 5
Figure 5
KEGG pathway enrichment analysis of differential metabolites between the control group and Pneumocystis-infected WT mice. (A) Positive and (B) negative ion modes.
Figure 6
Figure 6
mRNA expression levels of enzymes associated with tryptophan metabolism in the lungs in the control group and Pneumocystis-infected WT mice (***P < 0.001).
Figure 7
Figure 7
KEGG pathway enrichment analysis of differential metabolites between the Pneumocystis-infected WT mice and Pneumocystis-infected BAFF-R–/– mice. (A) Positive and (B) negative ion modes.
Figure 8
Figure 8
mRNA expression levels of enzymes associated with fatty acid metabolism in the lungs in the Pneumocystis-infected WT mice and Pneumocystis-infected BAFF-R–/– mice, and the correlation analysis of the mRNA expression levels of IL17A and SCD1 or FASN (*P < 0.05).
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