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Histoplasma capsulatum chemotypes I and II induce IL-8 secretion in lung epithelial cells in distinct manners
Cristiane Alcantara1, Bruna Rocha Almeida1, Bianca Carla Silva Campitelli Barros1
1Department of Microbiology, Immunology, and Parasitology, Escola Paulista de Medicina - Universidade Federal de São Paulo, São Paulo - SP, Brazil.
Abstract:
The cell wall is one of the most important structures of pathogenic fungi, enabling initial interaction with the host and consequent modulation of immunological responses. Over the years, some researchers have shown that cell wall components of Histoplasma capsulatum vary among fungal isolates, and one of the major differences is the presence or absence of α-(1,3)-glucan, classifying wild-type fungi as chemotypes II or I, respectively. The present work shows that an isolate of H. capsulatum chemotype I induced lower levels of interleukin (IL)-8 secretion by the lung epithelial cell line A549, when compared to chemotype II yeasts. Thus, we expected that the absence of α-glucan in spontaneous variant yeasts, which were isolated from chemotype II cultures, would modify IL-8 secretion by A549 cells, but surprisingly, these fungi promoted similar levels of IL-8 secretion as their wild-type counterpart. Furthermore, when using a specific inhibitor for Syk activation, we observed that this inhibitor reduced IL-8 levels in A549 cell cultures infected with wild type chemotype I fungi. This inhibitor failed to reduce this cytokine levels in A549 cell cultures infected with chemotype II and their spontaneous variant yeasts, which also do not present α-glucan on their surface. The importance of SFKs and PKC δ in this event was also analyzed. Our results show that different isolates of H. capsulatum modulate distinct cell signaling pathways to promote cytokine secretion in host epithelial cells, emphasizing the existence of various mechanisms for Histoplasma pathogenicity.
Insights
Histoplasma capsulatum cell wall variations, specifically the presence or absence of α-(1,3)-glucan, influence host immune responses. Different fungal chemotypes utilize distinct signaling pathways to modulate interleukin-8 secretion in lung epithelial cells.
Area of Science:
- Mycology
- Immunology
- Cell Biology
Background:
- The fungal cell wall is critical for pathogen-host interactions and immune modulation.
- Histoplasma capsulatum isolates differ in α-(1,3)-glucan presence, defining chemotypes I and II.
- Previous studies indicate variations in cell wall components affect host responses.
Purpose of the Study:
- To investigate the role of α-(1,3)-glucan absence in Histoplasma capsulatum variant yeasts on interleukin-8 (IL-8) secretion.
- To compare IL-8 secretion induced by chemotype I and II H. capsulatum isolates in lung epithelial cells.
- To elucidate the involvement of specific signaling pathways, including Syk, SFKs, and PKC δ, in H. capsulatum-mediated cytokine production.
Main Methods:
- Infection of A549 lung epithelial cells with H. capsulatum chemotype I, chemotype II, and spontaneous variant yeasts.
- Quantification of IL-8 secretion levels in response to fungal infection.
- Treatment with a Syk activation inhibitor to assess its impact on IL-8 secretion.
- Analysis of the roles of SFKs and PKC δ in the observed signaling events.
Main Results:
- H. capsulatum chemotype I induced lower IL-8 secretion than chemotype II.
- Spontaneous variant yeasts lacking α-glucan did not alter IL-8 secretion compared to their wild-type counterparts.
- Syk inhibition reduced IL-8 levels in chemotype I infections but not in chemotype II or variant infections.
- Distinct signaling pathways are modulated by different H. capsulatum isolates.
Conclusions:
- The absence of α-(1,3)-glucan in H. capsulatum variants does not uniformly affect IL-8 secretion.
- Syk-dependent pathways are involved in IL-8 induction by chemotype I fungi, but not by chemotype II or variants.
- Different H. capsulatum isolates employ diverse mechanisms to modulate host epithelial cell cytokine secretion, highlighting varied pathogenicity strategies.
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