The unresponsiveness of aged mice to polysaccharide antigens is a result of a defect in macrophage function

Chelvarajan, R. Lakshman; Collins, Sarah M.; Willigen, Juliana M. Van; Bondada, Subbarao

doi:10.1189/jlb.0804449

Cited by 124 publications

(108 citation statements)

References 54 publications

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“…Although germinal centers typically do not form in response to LPS, specific antibodies still have a higher affinity to LPS than NAbs (Bruderer et al, 1992). In mice, an age-associated decrease in antibody responses to Tindependent antigens, including LPS, has been reported (Chelvarajan et al, 2005). A similar result was found in a natural population of tree swallows (Tachycineta bicolor), where young and mid-age females injected with LPS mounted a specific antibody response, while the oldest individuals did not (Palacios et al, 2011).…”

Section: Introductionsupporting

confidence: 65%

Humoral immune responses are maintained with age in a long-lived ectotherm, the red-eared slider turtle

Zimmerman

Clairardin

Paitz

et al. 2012

Journal of Experimental Biology

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SUMMARYAging is typically associated with a decrease in immune function. However, aging does not affect each branch of the immune system equally. Because of these varying effects of age on immune responses, aging could affect taxa differently based on how the particular taxon employs its resources towards different components of immune defense. An example of this is found in the humoral immune system. Specific responses tend to decrease with age while non-specific, natural antibody responses increase with age. Compared with mammals, reptiles of all ages have a slower and less robust humoral immune system. Therefore, they may invest more in non-specific responses and thus avoid the negative consequences of age on the immune system. We examined how the humoral immune system of reptiles is affected by aging and investigated the roles of non-specific, natural antibody responses and specific responses by examining several characteristics of antibodies against lipopolysaccharide (LPS) in the red-eared slider turtle. We found very little evidence of immunosenescence in the humoral immune system of the red-eared slider turtle, Trachemys scripta, which supports the idea that non-specific, natural antibody responses are an important line of defense in reptiles. Overall, this demonstrates that a taxonʼs immune strategy can influence how the immune system is affected by age.

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Section: Introductionsupporting

confidence: 65%

Humoral immune responses are maintained with age in a long-lived ectotherm, the red-eared slider turtle

Zimmerman

Clairardin

Paitz

et al. 2012

Journal of Experimental Biology

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“…Cells were recovered from the interphase and washed with PBS. Lamina propria macrophages (LPMfs) were purified by positive selection from LP mononuclear cells using a magnetic cell separation system (MACS; Miltenyi Biotec, Auburn, CA) with antimouse CD11b microbeads, as described previously (16,17).…”

Section: Isolation Of Lamina Propria Macrophagesmentioning

confidence: 99%

Monocyte Chemoattractant Protein-1 Contributes to Gut Homeostasis and Intestinal Inflammation by Composition of IL-10–Producing Regulatory Macrophage Subset

Takada

Hisamatsu

Kamada

et al. 2010

The Journal of Immunology

128

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Lamina propria macrophages (LPMϕs) spontaneously produce large amounts of anti-inflammatory IL-10 and play a central role in regulation of immune responses against commensal bacteria. MCP-1 is a chemokine that plays an important role in recruitment of monocytes and macrophages to inflamed tissues. We demonstrated that, in addition to IL-10, LPMϕs produced large amounts of MCP-1, even in a steady state. MCP-1 deficiency caused impaired IL-10 production by LPMϕs and led to exacerbation of dextran sulfate sodium-induced acute colitis. As an explanation of this impaired IL-10 production by LPMϕs, we found that LPMϕs could be separated into two subsets with distinct side-scattered properties, namely LPMϕ1 (CD11b+F4/80+CD11c–SSChi) and LPMϕ2 (CD11b+F4/80+CD11c–SSClo). Unlike LPMϕ1, the LPMϕ2 subset migrated in response to MCP-1 and produced a larger amount of IL-10 in response to commensal bacteria. LPMϕs isolated from MCP-1–deficient mice produced less IL-10 as a consequence of the lack of the MCP-1–dependent LPMϕ2 population. This imbalanced composition in LPMϕ population may be involved in the susceptibility to DSS-induced colitis in MCP-1–deficient mice. Our results suggest that endogenous MCP-1 contributes to the composition of resident LPMϕ subsets in the intestine. Moreover, MCP-1–dependent LPMϕ2 subset may play an important role in maintenance of gut homeostasis in the steady state, and in the termination of excess inflammatory responses in the intestine, by producing IL-10.

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“…Cells were recovered from the interphase and washed with PBS. CLPM and splenic M were purified by positive selection from lamina propria mononuclear cells or unfractionated splenocytes using MACS CD11b microbeads (Miltenyi Biotec) as previously described (24,26).…”

Section: Isolation Of Colonic Lamina Propria M (Clpm) and Splenic Mmentioning

confidence: 99%

Abnormally Differentiated Subsets of Intestinal Macrophage Play a Key Role in Th1-Dominant Chronic Colitis through Excess Production of IL-12 and IL-23 in Response to Bacteria

Kamada

Hisamatsu

Okamoto

et al. 2005

The Journal of Immunology

192

185

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Disorders in enteric bacteria recognition by intestinal macrophages (Mφ) are strongly correlated with the pathogenesis of chronic colitis; however the precise mechanisms remain unclear. The aim of the current study was to elucidate the roles of Mφ in intestinal inflammation by using an IL-10-deficient (IL-10−/−) mouse colitis model. GM-CSF-induced bone marrow-derived Mφ (GM-Mφ) and M-CSF-induced bone marrow-derived Mφ (M-Mφ) were generated from bone marrow CD11b+ cells. M-Mφ from IL-10−/− mice produced abnormally large amounts of IL-12 and IL-23 upon stimulation with heat-killed whole bacteria Ags, whereas M-Mφ from wild-type (WT) mice produced large amounts of IL-10 but not IL-12 or IL-23. In contrast, IL-12 production by GM-Mφ was not significantly different between WT and IL-10−/− mice. In ex vivo experiments, cytokine production ability of colonic lamina propria Mφ (CLPMφ) but not splenic Mφ from WT mice was similar to that of M-Mφ, and CLPMφ but not splenic Mφ from IL-10−/− mice also showed abnormal IL-12p70 hyperproduction upon stimulation with bacteria. Surprisingly, the abnormal IL-12p70 hyperproduction from M-Mφ from IL-10−/− mice was improved by IL-10 supplementation during the differentiation process. These results suggest that CLPMφ and M-Mφ act as anti-inflammatory Mφ and suppress excess inflammation induced by bacteria in WT mice. In IL-10−/− mice, however, such Mφ subsets differentiated into an abnormal phenotype under an IL-10-deficient environment, and bacteria recognition by abnormally differentiated subsets of intestinal Mφ may lead to Th1-dominant colitis via IL-12 and IL-23 hyperproduction. Our data provide new insights into the intestinal Mφ to gut flora relationship in the development of colitis in IL-10−/− mice.

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The unresponsiveness of aged mice to polysaccharide antigens is a result of a defect in macrophage function

Cited by 124 publications

References 54 publications

Humoral immune responses are maintained with age in a long-lived ectotherm, the red-eared slider turtle

Humoral immune responses are maintained with age in a long-lived ectotherm, the red-eared slider turtle

Monocyte Chemoattractant Protein-1 Contributes to Gut Homeostasis and Intestinal Inflammation by Composition of IL-10–Producing Regulatory Macrophage Subset

Abnormally Differentiated Subsets of Intestinal Macrophage Play a Key Role in Th1-Dominant Chronic Colitis through Excess Production of IL-12 and IL-23 in Response to Bacteria

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