Dexamethasone disrupts skull bone marrow-dura mater border, prolonging parameningeal infection in mice intranasally inoculated with E. coli
Cai, Hanxiao LU ; Huang, Wenmian ; Li, Yicheng ; Du, Yutao ; Ye, Fanfan ; Liu, Tao ; Yang, Yiyi LU
; Xue, Xiaochang
and Feng, Guodong
(2025)
In Microbial Pathogenesis
206.
- Abstract
The incidence of parameningeal infection (PI) is increasing in the context of therapy-induced immunosuppression. PI often presents with atypical symptoms, leading to delayed diagnosis and intervention, and can result in severe neurological sequelae. However, current understanding of PI remains limited due to a lack of basic research on host-pathogen interactions. Here, we first established a transient PI model in immunocompetent adult mice by intranasally administering Escherichia coli (E. coli), without inducing bacteraemia or systemic infection. When dexamethasone, an immunosuppressive and anti-inflammatory agent, was co-administered, the model transitioned into a prolonged state. Immunofluorescence and flow cytometry analyses... (More)
The incidence of parameningeal infection (PI) is increasing in the context of therapy-induced immunosuppression. PI often presents with atypical symptoms, leading to delayed diagnosis and intervention, and can result in severe neurological sequelae. However, current understanding of PI remains limited due to a lack of basic research on host-pathogen interactions. Here, we first established a transient PI model in immunocompetent adult mice by intranasally administering Escherichia coli (E. coli), without inducing bacteraemia or systemic infection. When dexamethasone, an immunosuppressive and anti-inflammatory agent, was co-administered, the model transitioned into a prolonged state. Immunofluorescence and flow cytometry analyses revealed that dexamethasone prolonged PI by impairing innate immune-mediated clearance of E. coli at the skull bone marrow-dura mater border, which we identified as the initial immune barrier of the central nervous system (CNS). Specifically, dexamethasone inhibited the proliferation of Ly6C+ monocytes in the skull bone marrow and subsequently their influx to the dura mater, while also suppressing the functional shift of macrophages. These effects collectively hindered pathogen clearance and prolonged PI. Overall, our work established both transient and prolonged PI mouse models and explored how dexamethasone promotes PI progression. Our findings highlight the skull bone marrow-dura mater border as a critical frontline defence of the CNS, offering a potential target for the prophylaxis and therapy of PI and other CNS infections.
(Less)
- author
- Cai, Hanxiao
LU
; Huang, Wenmian
; Li, Yicheng
; Du, Yutao
; Ye, Fanfan
; Liu, Tao
; Yang, Yiyi
LU
; Xue, Xiaochang
and Feng, Guodong
- organization
- publishing date
- 2025-09
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Dexamethasone, Dura mater, Escherichia coli, Parameningeal infection, Skull bone marrow
- in
- Microbial Pathogenesis
- volume
- 206
- article number
- 107752
- publisher
- Academic Press
- external identifiers
-
- scopus:105006738183
- pmid:40441390
- ISSN
- 0882-4010
- DOI
- 10.1016/j.micpath.2025.107752
- language
- English
- LU publication?
- yes
- id
- 3b5bc644-5756-4d4b-8092-8703b2c32713
- date added to LUP
- 2025-07-16 14:58:52
- date last changed
- 2025-07-17 03:13:45
@article{3b5bc644-5756-4d4b-8092-8703b2c32713,
abstract = {{<p>The incidence of parameningeal infection (PI) is increasing in the context of therapy-induced immunosuppression. PI often presents with atypical symptoms, leading to delayed diagnosis and intervention, and can result in severe neurological sequelae. However, current understanding of PI remains limited due to a lack of basic research on host-pathogen interactions. Here, we first established a transient PI model in immunocompetent adult mice by intranasally administering Escherichia coli (E. coli), without inducing bacteraemia or systemic infection. When dexamethasone, an immunosuppressive and anti-inflammatory agent, was co-administered, the model transitioned into a prolonged state. Immunofluorescence and flow cytometry analyses revealed that dexamethasone prolonged PI by impairing innate immune-mediated clearance of E. coli at the skull bone marrow-dura mater border, which we identified as the initial immune barrier of the central nervous system (CNS). Specifically, dexamethasone inhibited the proliferation of Ly6C<sup>+</sup> monocytes in the skull bone marrow and subsequently their influx to the dura mater, while also suppressing the functional shift of macrophages. These effects collectively hindered pathogen clearance and prolonged PI. Overall, our work established both transient and prolonged PI mouse models and explored how dexamethasone promotes PI progression. Our findings highlight the skull bone marrow-dura mater border as a critical frontline defence of the CNS, offering a potential target for the prophylaxis and therapy of PI and other CNS infections.</p>}},
author = {{Cai, Hanxiao and Huang, Wenmian and Li, Yicheng and Du, Yutao and Ye, Fanfan and Liu, Tao and Yang, Yiyi and Xue, Xiaochang and Feng, Guodong}},
issn = {{0882-4010}},
keywords = {{Dexamethasone; Dura mater; Escherichia coli; Parameningeal infection; Skull bone marrow}},
language = {{eng}},
publisher = {{Academic Press}},
series = {{Microbial Pathogenesis}},
title = {{Dexamethasone disrupts skull bone marrow-dura mater border, prolonging parameningeal infection in mice intranasally inoculated with E. coli}},
url = {{http://dx.doi.org/10.1016/j.micpath.2025.107752}},
doi = {{10.1016/j.micpath.2025.107752}},
volume = {{206}},
year = {{2025}},
}