Atrophy of skin-draining lymph nodes predisposes for impaired immune responses to secondary infection in mice with chronic intestinal nematode infection

Abstract

Intestinal nematodes suppress immune responses in the context of allergy, gut inflammation, secondary infection and vaccination. Several mechanisms have been proposed for this suppression including alterations in Th2 cell differentiation and increased Treg cell suppressive function. In this study, we show that chronic nematode infection leads to reduced peripheral responses to vaccination because of a generalized reduction in the available responsive lymphocyte pool. We found that superficial skin-draining lymph nodes (LNs) in mice that are chronically infected with the intestinal nematode Heligmosomides polygyrus, do not reach the same cellularity as worm-free mice upon subsequent BCG infection in the skin. B cells and T cells, all declined in skin-draining LN of H. polygyrus-infected mice, resulting in LNs atrophy and altered lymphocyte composition. Importantly, anti-helminthic treatment improved lymphocyte numbers in skin-draining LN, indicating that time after de-worming is critical to regain full-scale LN cellularity. De-worming, and time for the skin LN to recover cellularity, also mended responses to Bacille Calmette-Guerin (BCG) in the LN draining the footpad injection site. Thus, our findings show that chronic nematode infection leads to a paucity of lymphocytes in peripheral lymph nodes, which acts to reduce the efficacy of immune responses at these sites.

Intestinal nematode infection exacerbates experimental visceral leishmaniasis

“…These divergent results may have several explanations such as the choice of model, infectious dose and the time of infection/s. While there are studies indicating systemic dissemination of both type 2 and regulatory responses after intestinal nematode infection, the effects are most evident when worm burdens are high and when the worm itself is in proximity to the secondary challenge …”

“…20 In contrast, preexisting, acute Strongyloides ratti infection was found not to affect L major lesions in C57BL/6 mice despite hampered IFNγ levels in draining lymph nodes. 21 burdens are high [24][25][26][27] and when the worm itself is in proximity to the secondary challenge. 24 Lymphocytes are rare in healthy hepatic tissue of young SPF mice, 28 and as expected, the H. polygyrus infection alone did not affect expression of T cell-associated mRNAs in the liver.…”

“…21 burdens are high [24][25][26][27] and when the worm itself is in proximity to the secondary challenge. 24 Lymphocytes are rare in healthy hepatic tissue of young SPF mice, 28 and as expected, the H. polygyrus infection alone did not affect expression of T cell-associated mRNAs in the liver. L donovani, on the other hand, propagates in the liver and causes leucocyte infiltration and an increase in T cell-associated transcript.…”

“…Less nos2 may indicate that granuloma formation was affected by the presence of worms. We recently proposed a mechanism where H polygyrus infection causes redistribution of lymphocytes from the periphery to lymphoid tissue draining the gut . Even though the duration of the Leishmania infection studied here was too short to detect bona fide granulomas, the lack of available immune cells may be part of the explanation to the lower cellular infiltration and altered cytokine profile in livers of coinfected mice.…”

Intestinal helminth infection transforms the CD4+ T cell composition of the skin

“…2,3 We and others have shown that worm infection can dampen immune responses to infection and vaccination in the skin. [4][5][6] Enhanced T helper-cell type 2 (TH2) and regulatory (TREG) responses are commonly suggested to drive the down-modulating effects of worms on subsequent immune responses. 2 Furthermore, we recently described how a chronic intestinal infection with the model worm pathogen Heligmosomoides polygyrus bakerii causes redistribution of circulating lymphocytes with accumulation of T cells in the mesenteric lymph nodes (mesLNs).…”