Loss of CD103+ DCs and Mucosal IL-17+ and IL-22+ Lymphocytes is Associated with Mucosal Damage in SIV Infection

HIV/SIV disease progression is associated with multifocal damage to the GI tract epithelial barrier that correlates with microbial translocation and persistent pathological immune activation but the underlying mechanisms remain unclear. Investigating alterations in mucosal immunity during SIV infection, we found that damage to the colonic epithelial barrier was associated with loss of multiple lineages of IL-17-producing lymphocytes, cells that microarray analysis showed express genes important for enterocyte homeostasis, including IL-22. IL-22-producing lymphocytes were also lost after SIV infection. Potentially explaining coordinate loss of these distinct populations, we also observed loss of CD103+ DCs after SIV infection which associated with loss of IL-17 and IL-22-producing lymphocytes. CD103+ DCs expressed genes associated with promotion of IL-17/IL-22+ cells, and co-culture of CD103+ DCs and naïve T-cells led to increased IL17A and RORc expression in differentiating T-cells. These results reveal complex interactions between mucosal immune cell subsets providing potential mechanistic insights into mechanisms of mucosal immune dysregulation during HIV/SIV infection, and offer hints for development of novel therapeutic strategies to address this aspect of AIDS virus pathogenesis

The Relationship Between Vestibular Sensory Integration and Prosthetic Mobility in Community Ambulators With Unilateral Lower Limb Amputation

Abstract Objective The modified Clinical Test of Sensory Interaction and Balance (mCTSIB) is used to clinically assess vestibular sensory integration (VSI), the process by which the central nervous system integrates vestibular afference to maintain balance. The rate and effects of impaired VSI (IVSI) on prosthetic mobility in people with lower limb amputation (LLA) is unknown. The objective of this study was to use the mCTSIB to classify VSI in active community ambulators with LLA and to examine the relationship between IVSI and prosthetic mobility, as measured by the Component Timed Up and Go (cTUG) test. Methods This was a cross-sectional study with a convenience sample of 130 community ambulators with unilateral LLA. Classification of VSI was determined based on a time-based pass/fail mCTSIB performance. Participants were classified as having normal sensory integration (NSI) if they could balance for 30 seconds in every mCTSIB condition. Participants who failed condition 4 exclusively were classified as IVSI. Prosthetic mobility, as measured by the cTUG, was compared between NSI and IVSI groups. Results Of the 130 participants, 29 (22%) were classified as IVSI and 95 (73%) were classified as having NSI. Prosthetic mobility significantly differed between IVSI and NSI groups, with IVSI participants performing all components of the cTUG significantly slower. Medium to large effect sizes were found between groups during cTUG. Conclusions These results suggest that 1 in 5 community ambulators with LLA have IVSI, with associated limitations in balance confidence and prosthetic mobility. Impact The ability to integrate vestibular information was found to have a strong relationship with prosthetic mobility in active community ambulators with LLA, especially with performing a 180-degree step turn. Physical therapists can use the mCTSIB to classify sensory integration during prosthetic rehabilitation and develop an appropriate balance intervention. Lay Summary Active adults with LLA can use information from their senses to maintain their standing balance. Adults with LLA who have difficulty balancing on foam with closed eyes were slower to get in and out of a chair, walk, and perform a 180-degree step turn

Exo-endocytic trafficking and the septin-based diffusion barrier are required for the maintenance of Cdc42p polarization during budding yeast asymmetric growth

The small GTPase Cdc42p is a master regulator of cell polarity. We analyzed Cdc42p localization using yeast mutants and found that endo-exocytic trafficking and septin-based diffusion barrier synergistically control Cdc42p polarization during asymmetric cell growth