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Herpes simplex virus type 1 dysregulates anti‐fungal defenses preventing monocyte activation and downregulating toll‐like receptor‐2
Author(s) -
Cermelli Claudio,
Orsi Carlotta Francesca,
Ardizzoni Andrea,
Lugli Enrico,
Cenacchi Valeria,
Cossarizza Andrea,
Blasi Elisabetta
Publication year - 2008
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2008.00074.x
Subject(s) - biology , herpes simplex virus , monocyte , phagocytosis , microbiology and biotechnology , cd38 , apoptosis , thp1 cell line , cell culture , virology , viral replication , virus , immunology , biochemistry , genetics , stem cell , cd34
We investigated the interplay occurring between pathogens in the course of dual infections, using an in vitro model in which the THP‐1 monocytic cell line is first infected with HSV‐1 and then exposed to Ca or Cn . These three pathogens share some pathogenic features: they cause opportunistic infections, target macrophages and are neurotropic. Here, we show that HSV‐1‐infected THP‐1 cells exhibited augmented phagocytosis against the two opportunistic fungi but reduced capability to counteract fungal infection: the better ingestion by monocytes was followed by facilitated fungal survival and replication. Reduced IL‐12 production was also observed. Cytofluorimetric analysis showed that HSV‐1‐infected monocytes exhibit: (i) downregulated TLR‐2 and TLR‐4, critical structures in fungal recognition; (ii) reduced expression of CD38 and CD69, known to be important markers of monocyte activation; and (iii) enhanced expression of apoptosis and necrosis markers, in the absence of altered cell proliferation. Overall, these findings imply that HSV‐1 infection prevents monocyte activation, thus leading to a significant dysfunction of the monocyte‐mediated anti‐ Candida response; HSV‐1 induced apoptosis and necrosis of monocytes further contribute to this impairment.