Basis for the Age‐related Decline in Intestinal Mucosal Immunity

Abstract

The elderly are characterized by mucosal immunosenescence and high rates of morbidity and mortality associated with infectious diseases of the intestinal tract. Little is known about how the differentiation of immunoglobulin A (IgA) plasma cells in Peyer's patches (PPs) and their subsequent homing to the small intestinal lamina propria (LP) is affected by aging. Quantitative immunohistochemical analyses demonstrated a 2-fold increase in the number of IgA þ cells in the PPs, coupled with significant declines in the numbers of IgA þ and antibody-positive cells in the intestinal LP of senescent rats compared to young adult animals. These data suggest that aging diminishes the emigration of IgA immunoblasts from these lymphoid aggregates, as well as their migration to the intestinal LP. Flow cytometry and lymphocyte adoptive transfer studies showed 3-to 4-fold age-related declines in the homing of antibody-containing cells and mesenteric lymph node lymphocytes to the small intestines of rhesus macaques and rats, respectively. The number of peripheral blood IgA immunoblasts expressing the homing molecule a4b7 declined 30% in senescent rats. This was accompanied by a .17% decrease in the areal density of LP blood vessels staining positive for the cell adhesion molecule MAdCAM-1. Cumulatively, declines in expression of these homing molecules constitute a substantial age-related diminution of IgA immunoblast homing potential. In vitro antibody secretion by LP plasma cells, i.e. antibody secreted per antibody-positive cell, remains unchanged as a function of donor age. Intestinal mucosal immunosenescence is a consequence of reduced homing of IgA plasma cells to the intestinal LP as a result of declines in homing molecule expression.

Analysis of HIV/AIDS Epidemiology in Japan from 1985–2011-Infection Detection Pattern for Male Homosexuals Different from That for Male Heterosexuals but Similar to That for Females

“…One possible candidate hypothesis is as follows: Mucosal immunity, including neutralizing IgA, is involved in the defense against HIV (9) and immunity, including mucosal immunity, decreases with age (10)(11)(12). In that case, AIDS may develop earlier as the age advances, and the detection rate of``AIDS cases'' relative to that of``HIV cases'' will consequently increase with age.…”

Intermittent fasting favored the resolution of Salmonella typhimurium infection in middle-aged BALB/c mice

“…This suggests that S. typhimurium infection following intermittent fasting (1) did not counteract the effects of age on the down-modulation of α-and J-chain transcripts for specific IgA synthesis, probably because of decreasing the maturation of IgA immunoblasts (Schmucker et al 2003;Thoreux et al 2000), and (2) increased the level of total IgA. The latter increase probably resulted from a greater number of IgA+ plasma cells derived from an existing pool of IgA+ B cell clones, which would come from IgM+ B cell precursors that underwent IgA class switch recombination (Suzuki and Fagarasan 2009).…”

“…That is, switching to ad libitum feeding would reset circadian rhythms involved in the attenuation of aging, leading to a synchrony of metabolic and physiological events (Froy and Miskin 2010). The latter may underlie metabolic pathways for counteracting the deleterious effects of age on intestinal immunity, thus improving the IgA responses for bacterial resolution (Schmucker et al 2003;Michetti et al 1992;Wijburg et al 2006).…”

“…Susceptibility to infections by enteropathogenic agents in older animals results from dysfunctions in antigen uptake by M cells, antigen presentation, B isotype switching, IgA+ B cell maturation and homing, IgA+ plasma cell secretion, and IgA transport via pIgR (Schmucker et al 2003). A previous report showed an association between resistance to S. typhimurium infection and the intestinal generation of IgA (GodinezVictoria et al 2014).…”

Proliferation and Differentiation of Hematopoietic Cells and Preservation of Immune Functions

“…It is generally accepted that the development of age-associated alterations occurs earlier in the mucosal immune system than in the systemic immune compartment (Schmucker et al, 2003). The mucosal immune system of the intestinal epithelia contains a functionally specialized T-cell population known as intraepithelial lymphocytes (IELs).…”