Plasmodium chabaudi limits early Nippostrongylus brasiliensis-induced pulmonary immune activation and Th2 polarization in co-infected mice

Abstract

BackgroundLarvae of several common species of parasitic nematodes obligately migrate through, and often damage, host lungs. The larvae induce strong pulmonary Type 2 immune responses, including T-helper (Th)2 cells as well as alternatively activated macrophages (AAMφ) and associated chitinase and Fizz/resistin family members (ChaFFs), which are thought to promote tissue repair processes. Given the prevalence of systemic or lung-resident Type 1-inducing pathogens in geographical areas in which nematodes are endemic, we wished to investigate the impact of concurrent Type 1 responses on the development of these Type 2 responses to nematode larval migration. We therefore infected BALB/c mice with the nematode Nippostrongylus brasiliensis, in the presence or absence of Plasmodium chabaudi chabaudi malaria parasites. Co-infected animals received both infections on the same day, and disease was assessed daily before immunological measurements were taken at 3, 5, 7 or 20 days post-infection.ResultsWe observed that the nematodes themselves caused transient loss of body mass and red blood cell density, but co-infection then slightly ameliorated the severity of malarial anaemia. We also tracked the development of immune responses in the lung and thoracic lymph node. By the time of onset of the adaptive immune response around 7 days post-infection, malaria co-infection had reduced pulmonary expression of ChaFFs. Assessment of the T cell response demonstrated that the Th2 response to the nematode was also significantly impaired by malaria co-infection.ConclusionP. c. chabaudi co-infection altered both local and lymph node Type 2 immune activation due to migration of N. brasiliensis larvae. Given recent work from other laboratories showing that N. brasiliensis-induced ChaFFs correlate to the extent of long-term lung damage, our results raise the possibility that co-infection with malaria might alter pulmonary repair processes following nematode migration. Further experimentation in the co-infection model developed here will reveal the longer-term consequences of the presence of both malaria and helminths in the lung.

NK cells activated by Interleukin-4 in cooperation with Interleukin-15 exhibit distinctive characteristics

“…These results suggest that IL4-NK-like cells are also induced in an IL-4-dependent physiological condition. Previous studies reported that IL-4-expressing cells were increased in the lung from day 5 after the infection of Nb and, consequently, Th2 immune responses were induced (29,30). Therefore, we next analyzed NK cells in the lung and found that IL4-NK-like cells were also increased at days 9 after infection with Nb, whereas the number of total NK cells was not significantly changed (Fig.…”

“…Because IL4-NK cells were not induced by IL-13, the induction of IL4-NK-like cells is IL-4-dependent. It is known that IL-4-expressing cells are increased in the lung from day 5 after the infection of Nb, which results in the induction of Th2 immune responses (29,30). In the Nb infection model, the roles of NK cells remain largely unknown.…”

Acute helminth infection enhances early macrophage mediated control of mycobacterial infection

“…However, innate immunity induced by acute Nb infection enhancing immunity to a subsequent unrelated infection has been demonstrated previously. Acute Nb infection can enhance clearance of Plasmodium chabaudi parasites in mice through induction of non-specific IFN-g. 37 Although helminth-enhanced protection against M. tb has not been widely reported, early stage S. mansoni infections have been associated with BCG vaccination-driven protection against M. tb, but as S. mansoni infection progressed, protection against M. tb declined. 15 These observations are in agreement with our data, namely that the early response to Nb provides an environment suitable to the control of M. bovis BCG.…”

Relationship between Mycobacterium Tuberculosis and Hookworm Infections among School Children in Mbita, Kenya

“…For example, Th2-dependent eosinophilic pneumonia is frequently observed after infection with a significant number of helminths, such as filaria, hookworm, or A. lumbricoides. However, some reports have shown that T helper 1 (Th1), rather than Th2 cytokines, are produced from PBMCs derived from hookworm infected-individuals in endemic areas [15][16][17]. In endemic areas, people are frequently exposed to pathogens that induce a Th1 response before or after they are infected with helminths, which may be the reason why Th2 immune responses appear dampened, even in those co-infected with helminthes.…”

“…In endemic areas, people are frequently exposed to pathogens that induce a Th1 response before or after they are infected with helminths, which may be the reason why Th2 immune responses appear dampened, even in those co-infected with helminthes. Infection with protozoa or bacteria that can stimulate a Th1 response results in suppression of the Th2 response induced by helminthic infection in mouse models [15,18,19].…”