PMC

SYN1-expressing cells within the gut were significantly correlated with mRNA levels of (A) IL-17 and (B) MD-2 in the inguinal lymph node. Numbers of translocated E. coli within the lymph node were associated with mRNA levels (C) IL-17 and (D) MD-2.

Representative images of SYN1 expression in the gut of uninfected individuals (A, B) and HIV-1-infected persons in the presymptomatic stage of disease (C) and AIDS (D) were examined immunohistochemically (SYN1-positive cells appear brown while cell nuclei appear blue). (E) SYN1 expression was enumerated in each gut biopsy and reported as % tissue area positive for SYN1. The results are shown with significance where applicable (p < 0.05). Symbols: triangles and circles represent ileal and rectal biopsies, respectively, while the black bars denote the mean expression level of SYN1 in each stage of disease. Original magnifications: X200; scale bars: 50 µm.

(A) Numbers of translocated E. coli were significantly correlated with mRNA levels of Ki-67 in the inguinal lymph node. (B) Representative images of E. coli (red fluorescence) and Ki-67 positive cells (green fluorescence) in the inguinal lymph node of an HIV-1-infected individual in the AIDS stage of disease (B and C) and inguinal lymph node of an uninfected individual (D) were examined immunofluorescently. The image in (C) is an enlarged view of the area circled in white. The insets show the total numbers of cells (cell nuclei appear blue) in each image. (E) Numbers of translocated E. coli were significantly correlated with mRNA levels of IFN-α in the inguinal lymph node. Original magnifications: X200 (B, D, and insets) and X600 (C); scale bars: 20 µm (C) and 50 µm (B and D).

(A) Representative images of CLD2 expression in the ileum of an uninfected and HIV-1-infected individual in the acute stage of disease were examined immunohistochemically (CLD2-positive cells appear brown while cell nuclei appear blue). (B) CLD2 expression along the intestinal epithelium was quantified in each gut biopsy and reported as a range of % tissue perimeter positive for CLD2. Differences in CLD2 expression across stage were deemed significant (p = 0.0018). Symbols: triangles and circles represent ileal and rectal biopsies, respectively. (C) Representative images of claudin-1 expression in the ileum of an uninfected and HIV-1-infected individual in the presymptomatic stage of disease were examined immunohistochemically (Claudin-1-positive cells appear brown while cell nuclei appear blue). (D) Representative image of SYN1 and CLD2 expression in the rectum of an HIV-1-infected individual was examined immunofluorescently, showing the apical location of CLD2 (red) and basolateral location of SYN1 (green) (cell nuclei appear blue). Original magnifications: X200 (A and B), X600 (C); scale bars: 20 µm (C) and 50 µm (A and B).

(A) Representative optical images of E. coli (red fluorescence) and SYN1 expression (green fluorescence) in the gut of HIV-1-infected individuals in the presymptomatic and AIDS stages of disease were examined immunofluorescently. (B) SYN1-expressing cells within the gut were significantly correlated with numbers of translocated E. coli in the inguinal lymph node. (C) Representative image of cytokeratin expression (green fluorescence) and E. coli (red fluorescence) reveals translocation in the presence of intact epithelium in a local section of the ileum of an HIV-1-infected individual in the presymptomatic stage of disease (cell nuclei appear blue). Symbols: L represents the luminal space and yellow arrows denote translocated E. coli localized spatially with SYN1-expressing cells. Original magnifications: X600 (A), X200 (C); scale bars: 20 µm (A) and 50 µm (C).

SYN1 expression in the gut (A) and numbers of translocated E. coli in the inguinal lymph node (B) were inversely correlated with numbers of peripheral blood CD4⁺ T cells. (C and D) Representative images of CD4⁺ T cells (green fluorescence) and cleaved caspase 3 (an indicator of apoptosis, red fluorescence) in the paracortical T cell zone of inguinal lymph nodes reveal higher amounts of apoptosis and CD4⁺ T cell loss coincident with higher levels of microbial translocation. The insets show the total numbers of cells (cell nuclei appear blue) in each image. The black arrows in (B) denote the HIV-1-infected individuals used for lymphatic tissue analysis in (C) and (D). The yellow arrows in (C) and (D) highlight CD4⁺ T cells undergoing apoptosis. Original magnification: X400; scale bars: 50 µm.