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. 2025 May 9:15:1551080.
doi: 10.3389/fcimb.2025.1551080. eCollection 2025.

Human beta defensin-2 protects the epithelial barrier during methicillin-resistant Staphylococcus aureus infection in chronic rhinosinusitis with nasal polyps

Tengfei Tian #  1 , Szuyao Hsu #  1 , Qin Sun  1 , Yang Shi  1 , Xianyang Hu  2 , Yang Wu  3 , Keqing Zhao  1 , Chunquan Zheng  1
Affiliations

Human beta defensin-2 protects the epithelial barrier during methicillin-resistant Staphylococcus aureus infection in chronic rhinosinusitis with nasal polyps

Tengfei Tian et al. Front Cell Infect Microbiol. .

Abstract

Objective: We investigated the effect of human beta defensin-2 (hBD-2) on nasal epithelial barrier function with methicillin-resistant Staphylococcus aureus (MRSA) infection in chronic rhinosinusitis with nasal polyps (CRSwNP).

Methods: The expression of hBD-2 was measured in nasal polyps (NPs) from CRSwNP. MRSA was treated with different concentrations of hBD-2 to assess the invasive ability. Primary human nasal epithelial cells (HNECs) cultured at the air-liquid interface (ALI) were pre-incubated with or without hBD-2 prior to MRSA infection. The cell viability, the epithelial cell integrity, and the tight junction (TJ) expression were evaluated.

Results: The expression of hBD-2 in the CRSwNP group was higher than that in the control group. In addition, the hBD-2 protein was negatively correlated with the Lund-Mackay CT score and was positively correlated with the neutrophil levels in CRSwNP. The presence of hBD-2 significantly reduced the invasive ability of MRSA in HNECs. MRSA decreased the epithelial cell integrity by diminishing the protein expression of occludin and zonula occludens-1 (ZO-1). Furthermore, hBD-2 prevented the MRSA-induced barrier disruption by increasing the mucosal permeability and the expression of occludin and ZO-1.

Conclusion: The results suggest that hBD-2 may partially attenuate the epithelial barrier disruption induced by MRSA, indicating the protective effect of hBD-2 on S. aureus infection.

Keywords: chronic rhinosinusitis with nasal polyps; epithelial barrier; human beta defensin-2; methicillin-resistant Staphylococcus aureus; tight junctions.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Expression levels of human hBD-2 in the nasal tissues of the control and of CRSwNP. (A) Representative immunofluorescence images of the hBD-2 protein (red color) in patients with CRSwNP compared with the control. (B) Quantitative analysis of the TFI of hBD-2 in patients with CRSwNP compared with the control. (C) Expression of hBD-2 mRNA in patients with CRSwNP compared with the control. TFI, TFI. Data are expressed as the mean ± SD. ***p < 0.001. Scale bar, 20 μm.
Figure 2
Figure 2
Correlation between human beta defensin-2 (hBD-2) protein expression and chronic rhinosinusitis with nasal polyps (CRSwNP) severity. (A) The hBD-2 protein levels were negatively correlated with the Lund–Mackay CT score. (B, C) The hBD-2 protein levels were positively correlated with the peripheral blood neutrophil counts (×109/L) and the peripheral blood neutrophil percentage (NEU%). Data were analyzed using nonparametric Spearman’s correlation. NEU, neutrophil; TFI, total fluorescence intensity.
Figure 3
Figure 3
Effect of human beta defensin-2 (hBD-2) on the growth curves and invasion profile of Staphylococcus aureus. (A) S. aureus USA500 was treated with hBD-2 at 5 and 10 μg for 24 h. The growth of their planktonic cells was determined by optical density at 600 nm (OD600). (B, C) S. aureus USA500 adhesion and internalization assay. The number of bacteria was determined by host cell lysis, plating, and counting of the colony forming units (CFU) per milliliter. (D) S. aureus USA500 Transwell invasion assay. The number of bacteria able to cross the nasal epithelial barrier was determined by plating the yeast in the basolateral site and counting the CFU per milliliter. Data are expressed as the mean ± SD. *p < 0.05, **p < 0.01.
Figure 4
Figure 4
The Staphylococcus aureus-induced barrier function was suppressed by human beta defensin-2 (hBD-2) in human nasal epithelial cells (HNECs). (A, B) The viability of HNECs was measured using the CCK-8 assay (A) and the lactate dehydrogenase (LDH) levels (B). (C, D) Epithelial permeability (C) and transepithelial electrical resistance (D) in HNECs stimulated with S. aureus USA500 with and without hBD-2 protein. Data are expressed as the mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001. TEER, transepithelial electrical resistance; LDH, lactate dehydrogenase.
Figure 5
Figure 5
Human beta defensin-2 (hBD-2) attenuates the Staphylococcus aureus-induced disruption of tight junctions. (A, B) Representative immunofluorescence images of occludin (A) and ZO-1 (B) protein production (red color) in human nasal epithelial cells (HNECs) after treatment. (C, D) Quantified total fluorescence intensity (TFI) of occludin (C) and ZO-1 (D). (E, F) Relative mRNA expression of occludin (E) and ZO-1 (F). Data are expressed as the mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001. TFI, total fluorescence intensity. Scale bar, 5 μm.
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