Roles of Host Phospholipase D during <i>Aspergillus fumigatus</i> Infection in Mice
<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d1447663e166"> <!-- named anchor --> </a> <h5 class="section-title...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Compuscript Ltd
2023-04-01
|
| Series: | Zoonoses |
| Online Access: | https://www.scienceopen.com/hosted-document?doi=10.15212/ZOONOSES-2022-0044 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | <div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section">
<a class="named-anchor" id="d1447663e166">
<!--
named anchor
-->
</a>
<h5 class="section-title" id="d1447663e167">Objective:</h5>
<p dir="auto" id="d1447663e169">
<i>Aspergillus fumigatus</i> infection in the lungs is accompanied by the recruitment of innate immune cells,
phagocytosis, and the release of inflammatory factors. Phospholipase D (PLD) is a
key regulator of cell migration and phagocytosis, but the effect of PLD deficiency
on antifungal infection in animals is unknown. This study aims to investigate the
impact of PLD on the host immune response to
<i>A. fumigatus</i> infection under either immunocompetent or immunosuppressed status.
</p>
</div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section">
<a class="named-anchor" id="d1447663e177">
<!--
named anchor
-->
</a>
<h5 class="section-title" id="d1447663e178">Methods:</h5>
<p dir="auto" id="d1447663e180">The invasive pulmonary aspergillosis mouse model was created using a modified protocol
with immunosuppression by steroids. For collection of bronchoalveolar lavage fluid
(BALF) from mice, the lungs were washed eight times with 0.5 ml of PBS. Total cell
counts in BALF were determined using a Coulter Counter. The content of alveolar macrophages,
neutrophils, and monocytes in BALF was examined by flow cytometry and analyzed by
FlowJo V10 software. Multiplex immunoassays were used to determine the concentrations
of inflammatory cytokines in BALF.
</p>
</div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section">
<a class="named-anchor" id="d1447663e182">
<!--
named anchor
-->
</a>
<h5 class="section-title" id="d1447663e183">Results:</h5>
<p dir="auto" id="d1447663e185">In immunocompetent mice, alveolar macrophages were the major cell population in BALF
after
<i>A. fumigatus</i> infection, and a number of neutrophils and monocytes were recruited in the alveoli.
Loss of both
<i>pld1</i> and
<i>pld2</i> genes did not affect the content of alveolar macrophages, neutrophils, or monocytes
in BALF. Under immunosuppression induced by hydrocortisone acetate,
<i>pld1
<sup>-/-</sup>pld2
<sup>-/-</sup>
</i> mice showed higher mortality after
<i>A. fumigatus</i> infection and had a higher fungal burden and much lower number of prominent focal
areas of dense inflammatory infiltrates in lung tissue than wild type mice. Moreover,
interleukin (IL)-12p40 significantly decreased, and IL-10 markedly increased, in BALF
from
<i>pld1</i>
<sup>-/-</sup>
<i>pld2</i>
<sup>-/-</sup> mice after infection.
</p>
</div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section">
<a class="named-anchor" id="d1447663e221">
<!--
named anchor
-->
</a>
<h5 class="section-title" id="d1447663e222">Conclusion:</h5>
<p dir="auto" id="d1447663e224">Our findings revealed that, during
<i>A. fumigatus</i> infection, deficiency in both
<i>pld1</i> and
<i>pld2</i> in mice was not conducive to the infiltration of inflammatory cells into lung tissue
but promoted the release of IL-10 and blocked the release of IL-12, thereby increasing
fungal burden and mortality.
</p>
</div> |
|---|---|
| ISSN: | 2737-7466 2737-7474 |