Histoplasma capsulatum chemotypes I and II induce IL-8 secretion in lung epithelial cells in distinct manners

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.

Paracoccidioides brasiliensis downmodulates α3 integrin levels in human lung epithelial cells in a TLR2-dependent manner

“…Our data have demonstrated that different fungal species promote cytokine secretion in lung epithelial cell in distinct manners. In fact, we verified that the stimulation mechanism of cytokine release differs even among isolates of the same species 12 , 13 .…”

“…Over the past years, our research group has focused on studying the lung epithelial cell responses to fungal infections, especially regarding the mechanisms involved in the release of inflammatory cytokines induced by yeasts of Paracoccidioides or Histoplasma capsulatum [7][8][9][10][11][12][13] . Our data have demonstrated that different fungal species promote cytokine secretion in lung epithelial cell in distinct manners.…”

Paracoccidioides brasiliensis Induces α3 Integrin Lysosomal Degradation in Lung Epithelial Cells

“…The goal of our research group has been to understand the responses of human lung epithelial cells after interaction with the human respiratory pathogenic fungi Paracoccidioides and Histoplasma capsulatum [ 4 , 15 , 16 , 23 , 24 , 26 , 36 , 37 , 38 , 39 ]. We have observed over the years that the integrin family receptors of lung epithelial cells participate in fungal adhesion and cytokine secretion during interaction with Paracoccidioides yeasts [ 15 , 16 , 23 ].…”