Relative mRNA Expression Levels of Restriction Factors and Antiviral Genes in Fetal and Adult Human Monocytes and Monocyte-Derived Macrophages.
Among untreated HIV-infected pregnant women, the frequency of mother-to-child transmission of HIV is low (5-10%), with most infections occurring at or after birth. Given findings that fetal and adult monocytes are distinct from one another in terms of basal transcriptional profiles, and in phosphorylation of signal transducer and activators of transcription in response to cytokines, we hypothesized that fetal CD14+CD16- monocyte and monocyte-derived macrophages (MDMs) might, compared to their adult counterparts, express higher levels of transcripts for restriction factors and antiviral factors at baseline and/or after stimulation with cytokines that might be induced upon transmission of HIV in utero, for example, IFNα, IFNγ, and IL-6. We carried out these experiments and noted that a few genes, including APOBEC3B, APOBEC3C, and IFITM2, were expressed to a greater degree in fetal monocytes compared to adults. Similarly, the expression levels of APOBEC3F and TRIM32 were greater in fetal MDMs. However, most of these differences were not observed after stimulation with cytokines and the vast majority of antiviral genes were more highly expressed in adults. Therefore, the results of this study are not consistent with the hypothesis that increased expression of antiviral genes in fetal myeloid cells confers immune protection to fetuses in utero.
1 Division of Experimental Medicine, Department of Medicine, University of California San Francisco (UCSF), San Francisco, California.
Karen
K
Trang
2 Department of Microbiology, Immunology and Tropical Medicine, The George Washington University , Washington, District of Columbia.
Rui André
RA
Raposo
1 Division of Experimental Medicine, Department of Medicine, University of California San Francisco (UCSF), San Francisco, California.
Margaret M
MM
Lowe
1 Division of Experimental Medicine, Department of Medicine, University of California San Francisco (UCSF), San Francisco, California.
Elisabeth R
ER
Krow-Lucal
1 Division of Experimental Medicine, Department of Medicine, University of California San Francisco (UCSF), San Francisco, California.
Wes
W
Yonemoto
2 Department of Microbiology, Immunology and Tropical Medicine, The George Washington University , Washington, District of Columbia.
Vinicius D
VD
Cabido
1 Division of Experimental Medicine, Department of Medicine, University of California San Francisco (UCSF), San Francisco, California.
Devi
D
SenGupta
1 Division of Experimental Medicine, Department of Medicine, University of California San Francisco (UCSF), San Francisco, California.
Joseph M
JM
McCune
D000328:Adult; D002478:Cells, Cultured; D005260:Female; D005333:Fetus; D020869:Gene Expression Profiling; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis*
D007155:Immunologic Factors; D012333:RNA, Messenger
interferon; macrophage; monocyte; restriction factor