TY - JOUR
T1 - Herpes simplex virus type 1 dysregulates anti-fungal defenses preventing monocyte activation and downregulating toll-like receptor-2
AU - Cermelli, Claudio
AU - Orsi, Carlotta Francesca
AU - Ardizzoni, Andrea
AU - Lugli, Enrico
AU - Cenacchi, Valeria
AU - Cossarizza, Andrea
AU - Blasi, Elisabetta
PY - 2008/12
Y1 - 2008/12
N2 - We investigated the interplay occurring between pathogens in the course of dual infections, using an in vitro model inwhich the THP-1 monocytic cell line is first infectedwith 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 phagocytosisagainstthetwoopportunisticfungibutreducedcapabilityto counteractfungal infection:the better ingestion bymonocytes was followed by facilitated fungal survival and replication. Reduced IL-12 productionwas also observed.Cytofluorimetric analysis showed that HSV-1-infectedmonocytes 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 ofmonocyte 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.
AB - We investigated the interplay occurring between pathogens in the course of dual infections, using an in vitro model inwhich the THP-1 monocytic cell line is first infectedwith 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 phagocytosisagainstthetwoopportunisticfungibutreducedcapabilityto counteractfungal infection:the better ingestion bymonocytes was followed by facilitated fungal survival and replication. Reduced IL-12 productionwas also observed.Cytofluorimetric analysis showed that HSV-1-infectedmonocytes 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 ofmonocyte 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.
KW - Candida albicans
KW - Herpes simplex virus type 1 (HSV-1)
KW - Innate immunity
KW - Monocyte
UR - http://www.scopus.com/inward/record.url?scp=59449098398&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59449098398&partnerID=8YFLogxK
U2 - 10.1111/j.1348-0421.2008.00074.x
DO - 10.1111/j.1348-0421.2008.00074.x
M3 - Article
C2 - 19120971
AN - SCOPUS:59449098398
VL - 52
SP - 575
EP - 584
JO - Microbiology and Immunology
JF - Microbiology and Immunology
SN - 0385-5600
IS - 12
ER -