Th17 cells, Job's syndrome and HIV: opportunities for bacterial and fungal infections.
OBJECTIVE
Patients with hyper IgE syndrome (HIES) share with HIV patients a predisposition to infections, including candidiasis in autosomal dominant HIES (AD-HIES) and molluscum contagiosum and other viral infections in other disorders of elevated IgE with infectious predilections. This review highlights the underlying pathogenesis of these diseases and their relevance to HIV infection.


RESULTS
Patients with mutations in STAT3, who lack Th17 cells, develop AD-HIES, whereas other disorders of elevated IgE may be caused by mutations in Tyk2 or DOCK8, the latter of which is associated with decreased expansion of CD8 more so than CD4 T cells. Recent studies on patients with recurrent mucocutaneous candidiasis have led to the discovery of mutations in CARD9 and DECTIN-1, genes key to the production of the Th17-driving cytokines IL-1beta, IL-6, and IL-23. Studies of the peripheral blood of HIV-positive patients have shown a decreased Th17:Th1 ratio, and Th17 cells were preferentially depleted from the gastrointestinal tract within weeks of simian immunodeficiency virus infection in rhesus macaques.


CONCLUSIONS
The consequences of inadequate Th17 production in primary immunodeficiency syndromes illustrate the role of Th17 cells in controlling pathogens to which HIV-positive individuals are susceptible. Further understanding of the pathogenesis of opportunistic disease in HIV infection will probably require exploring the role of Th17 cells.
Milner
Joshua D
JD
Allergic Inflammation Unit, Laboratory of Allergic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Sandler
Netanya G
NG
Douek
Daniel C
DC
D053468:CARD Signaling Adaptor Proteins / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D053583:Interleukin-1beta / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007589:Job Syndrome / Q000276:immunology* / Q000473:pathology; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000172:deficiency / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D053634:TYK2 Kinase / Q000235:genetics; D000099181:Dectin-1
D053468:CARD Signaling Adaptor Proteins; D020662:Guanine Nucleotide Exchange Factors; D007073:Immunoglobulin E; D053583:Interleukin-1beta; D053759:Interleukin-23; D015850:Interleukin-6; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050796:STAT3 Transcription Factor; D053634:TYK2 Kinase; D000099181:Dectin-1; C505855:CARD9 protein, human; C516591:DOCK8 protein, human; C494086:STAT3 protein, human; C070139:TYK2 protein, human