Distinct regulation of HLA class II and class I cell surface expression in the THP-1 macrophage cell line after bacterial phagocytosis

Abstract

Expression of HLA and CD1b molecules was investigated in the THP-1 macrophage cell line within 2 weeks following phagocytosis of mycobacteria or Escherichia coli. During the first 2-3 days, cell surface expression of HLA class II and CD1b was drastically down-modulated, whereas HLA class I expression was up-modulated. In the following days both HLA class II and CD1b expression first returned to normal, then increased and finally returned to normal with kinetics similar to that observed for the steadily increased HLA class I. The initial down-modulation of HLA class II and CD1b cell surface antigens was absolutely dependent on phagocytosis of bacteria. Further studies indicated that initial HLA class II cell surface down-modulation (1) was not due to reduced transcription or biosynthesis of mature HLA class II heterodimers, (2) was only partially, if at all, rescued by treatment with IFN-gamma, although both mRNA and corresponding intracellular proteins increased up to sixfold with respect to untreated cells, and (3) resulted in failure of THP-1 cells to process and present mycobacterial antigens to HLA-DR-restricted antigen-specific T cell lines. The existence of a transient block of transport of mature HLA class II heterodimers to the cell surface in the first days after phagocytosis of bacteria may have negative and positive consequences: it decreases APC function early but it may increase it later by favoring optimal loading of bacterial antigens in cellular compartments at high concentration of antigen-presenting molecules.

Major Histocompatibility Complex Class II Transactivator Inhibits Cysteine-rich 61 Expression in Osteoblastic Cells and Its Implication in the Pathogenesis of Periapical Lesions

“…Because CIITA plays a central role in the expression of MHC class II genes that are crucial to the protective immune responses mounted by the host, many pathogens have developed ways of interfering with the function or expression of CIITA (30). For example, phagocytosis of gram-negative bacteria (eg, Escherichia coli) and mycobacteria by human macrophages is accompanied by the down-regulation of MHC class II molecules as a consequence of the reduced transcription of CIITA (31). Viruses and bacteria can interfere at various steps of the pathway that mediates the induction of CIITA expression in immune cells by interferon-g (20).…”

HIV-1 Tat mutants in the cysteine-rich region downregulate HLA class II expression in T lymphocytic and macrophage cell lines

“…Indeed we could show that the antigen processing and presenting competence of the THP-1 macrophage cell line was severely hampered by the Tat mutants. This was best appreciated in IFN-+ -treated THP-1 cells, as normal cells did not display detectable antigen presenting capacity (this study and [28]). In fact, the HLA class II down-modulation brought about by the Tat mutants quantitatively correlated with the impairment in APC functions.…”

Stimulation of Human Monocytes with the Gram-Positive Vaccine VectorStreptococcus gordonii

“…The expression of costimulatory molecules, such as CD80 and CD86, also increased following 96 h of bacterial stimulation. Interestingly, the expression of HLA-DR was down-regulated by bacterial treatment, as previously observed with heat-killed Mycobacterium bovis and Escherichia coli (5). Using peripheral blood monocytes we have demonstrated that the phenotypic modifications observed following bacterial stimulation were not restricted to the monocytic THP-1 cell line.…”