Effects of Ageing on the Immunoregulation of Parasitic Infection

Abstract

The plethora of changes associated with immunosenescence radically alters virtually all aspects of immune responsiveness. How this transformation effects resolution of an infectious challenge is addressed in this study. A well-established infection model was used; Trichuris muris, a cecum-dwelling helminth, is natural to mice, and infection in different strains results in clearly polarized responses. A dominating T helper 2 (Th2) response orchestrates immunity, whereas a Th1 response will result in susceptibility. Mice between 19 and 28 months old were more susceptible to infection, whereas 3-month-old mice of the same strain demonstrated the resistant phenotype. The cytokine response made by these aged mice was clearly altered at the site of infection, and within the local draining lymph nodes higher Th1 and lower Th2 cytokine levels were found, both at the protein and RNA level. Confirming these changes, aged mice also showed a delayed parasite-specific immunoglobulin G1 response and intestinal mastocytosis, both of which are driven by Th2 cytokines. To address possible causes of the observed immune deviation, purified CD4 cells from both young and aged mice were stimulated in vitro. Cells from aged mice did not respond to stimulation via CD28 and in vitro were less able to proliferate and polarize into Th2 cells; Th1 polarization was found to be normal. Together these data suggest that changes in cytokine phenotype, particularly CD4 cells, contribute to the observed age-associated switch from T. muris resistance to susceptibility.

Imported Amoebic Liver Abscess in France

“…For elderly patients, alteration of immunity could be determined as a factor to develop a bigger abscess than for younger patients. This could be explained by the effects of immunosenescence [21]. We have also shown that laboratory findings, especially regarding leucocytosis, C Reactive Protein and hemoglobin, were identical for large and small abscesses.…”

Intramuscular immunization with p36(LACK) DNA vaccine induces IFN-γ production but does not protect BALB/c mice against Leishmania chagasi intravenous challenge

“…This phenomenon may be caused by the response induced by the p36(LACK) DNA vaccine associated with a change in cytokine production that happens in older mice. Humphreys and Grencis (2002) have shown that older mice (between 19 and 28 months old) are more susceptible to Trichuris muris infection than younger mice (3 months old), and this is associated with a higher IFN-γ and IL-12 production and a lower IL-4 and IL-5 production by lymph node cells. It is possible that the age difference due to the waiting period before the challenge infection may have influenced the cytokine pattern in response to L. chagasi, leading to a stronger type 1 response in older mice.…”

The Aging Immune System and Its Relationship to the Development of Chronic Obstructive Pulmonary Disease

“…A prime example of such dysregulation is the increased storage of ROS and impaired apoptosis found in senescent neutrophils as described above. Studies have also suggested that persistent herpes infection, cytomegalovirus (CMV) infection, or parasite antigens may significantly contribute to the increased levels of proinflammatory factors and contribute to a number of negative clinical consequences (62)(63)(64)(65). Together, persistent immunologic dysregulation and abnormal responses to autoantigens may help explain the increased risk of autoimmune diseases in the elderly during immunosenescence, but exactly which factors are most important and what causes these age-associated changes remains largely unclear.…”