Herpes simplex virus type 1 dysregulates anti-fungal defenses preventing monocyte activation and downregulating toll-like receptor-2.
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.
Cermelli
Claudio
C
Department of Public Health Sciences, University of Modena and Reggio Emilia, Modena, Italy. claudio.cermelli@unimore.it
Orsi
Carlotta Francesca
CF
Ardizzoni
Andrea
A
Lugli
Enrico
E
Cenacchi
Valeria
V
Cossarizza
Andrea
A
Blasi
Elisabetta
E
D017209:Apoptosis; D045744:Cell Line, Tumor; D003454:Cryptococcus / Q000276:immunology*; D015536:Down-Regulation; D006561:Herpes Simplex / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D010587:Phagocytosis; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D018664:Interleukin-12