Cooperative Role of Macrophages and Neutrophils in Host Antiprotozoan Resistance in Mice Acutely Infected with<i>Cryptosporidium parvum</i>

Takeuchi, Dan; Jones, Vickie C; Kobayashi, Makiko; Suzuki, Fujio

doi:10.1128/iai.00112-08

Cited by 37 publications

(31 citation statements)

References 49 publications

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“…Macrophages have been shown to produce large amounts of IFN-␥ in vitro when stimulated with a combination of IL-12 and IL-18 (22), both of which are expressed during cryptosporidial infection (16,26). In relation to our findings, other workers recently reported that the transference of peritoneal macrophages from C. parvum-infected mice to immunocompromised mice with a macrophage deficiency allowed the recipients to be resistant to infection with the parasite, and in vitro studies suggested that IFN-␥ from neutrophils might be involved in activation of the macrophages (25). DCs might also have an important protective role in this respect, as they have been found to be a potent source of IFN-␥ when activated by cytokines (11).…”

Section: Discussionsupporting

confidence: 84%

Roles for NK Cells and an NK Cell-Independent Source of Intestinal Gamma Interferon for Innate Immunity toCryptosporidium parvumInfection

et al. 2009

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A gamma interferon (IFN-␥)-dependent innate immune response operates against the intestinal parasiteCryptosporidium parvum in T-and B-cell-deficient SCID mice. Although NK cells are a major source of IFN-␥ in innate immunity, their protective role against C. parvum has been unclear. The role of NK cells in innate immunity was investigated using Rag2 ؊/؊ mice, which lack T and B cells, and Rag2 ؊/؊ ␥ c ؊/؊ mice, which, in addition, lack NK cells. Adult mice of both knockout lines developed progressive chronic infections; however, on most days the level of oocyst excretion was higher in Rag2 ؊/؊ ␥ c ؊/؊ mice and these animals developed morbidity and died, whereas within the same period the Rag2 ؊/؊ mice appeared healthy. Neonatal mice of both mouse lines survived a rapid onset of infection that reached a higher intensity in Rag2 ؊/؊ ␥ c ؊/؊ mice. Significantly, similar levels of intestinal IFN-␥ mRNA were expressed in Rag2 ؊/؊ and Rag2 ؊/؊ ␥ c ؊/؊ mice. Also, infections in each mouse line were exacerbated by treatment with anti-IFN-␥ neutralizing antibodies.

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Section: Discussionsupporting

confidence: 84%

Roles for NK Cells and an NK Cell-Independent Source of Intestinal Gamma Interferon for Innate Immunity toCryptosporidium parvumInfection

et al. 2009

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“…Although NET formation was initially characterized in response to bacteria and protozoa [20, 27], it has also been reported for larger multi-cellular pathogens including fungi and three species of parasitic nematodes [19, 24, 25]. Our initial experiments co-culturing B .…”

Section: Resultsmentioning

confidence: 99%

“…stercoralis L3 [23]. In several studies PMNs have been shown to co-operate with monocytes or macrophages in immunity against parasites, including helminths [18, 24–27]. …”

Section: Introductionmentioning

confidence: 99%

Human Leukocytes Kill Brugia malayi Microfilariae Independently of DNA-Based Extracellular Trap Release

et al. 2017

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BackgroundWuchereria bancrofti, Brugia malayi and Brugia timori infect over 100 million people worldwide and are the causative agents of lymphatic filariasis. Some parasite carriers are amicrofilaremic whilst others facilitate mosquito-based disease transmission through blood-circulating microfilariae (Mf). Recent findings, obtained largely from animal model systems, suggest that polymorphonuclear leukocytes (PMNs) contribute to parasitic nematode-directed type 2 immune responses. When exposed to certain pathogens PMNs release extracellular traps (NETs) in the form of chromatin loaded with various antimicrobial molecules and proteases.Principal findingsIn vitro, PMNs expel large amounts of NETs that capture but do not kill B. malayi Mf. NET morphology was confirmed by fluorescence imaging of worm-NET aggregates labelled with DAPI and antibodies to human neutrophil elastase, myeloperoxidase and citrullinated histone H4. A fluorescent, extracellular DNA release assay was used to quantify and observe Mf induced NETosis over time. Blinded video analyses of PMN-to-worm attachment and worm survival during Mf-leukocyte co-culture demonstrated that DNase treatment eliminates PMN attachment in the absence of serum, autologous serum bolsters both PMN attachment and PMN plus peripheral blood mononuclear cell (PBMC) mediated Mf killing, and serum heat inactivation inhibits both PMN attachment and Mf killing. Despite the effects of heat inactivation, the complement inhibitor compstatin did not impede Mf killing and had little effect on PMN attachment. Both human PMNs and monocytes, but not lymphocytes, are able to kill B. malayi Mf in vitro and NETosis does not significantly contribute to this killing. Leukocytes derived from presumably parasite-naïve U.S. resident donors vary in their ability to kill Mf in vitro, which may reflect the pathological heterogeneity associated with filarial parasitic infections.Conclusions/SignificanceHuman innate immune cells are able to recognize, attach to and kill B. malayi microfilariae in an in vitro system. This suggests that, in vivo, the parasites can evade this ability, or that only some human hosts support an infection with circulating Mf.

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“…Neutrophils have been shown to play an active role in the control of infections with specific and distinct pathogens such as Legionella (17), Toxoplasma (27), Mycobacterium (28), Entamoeba (29), Histoplasma (30), and Cryptosporidium (31). BALB/c mice infected in the ear dermis with L. braziliensis develop cutaneous lesions at the site of inoculation and histological analyses of infected ear sections have demonstrated a constant recruitment of neutrophils to the inoculation site (14).…”

Section: Discussionmentioning

confidence: 99%

Neutrophils and Macrophages Cooperate in Host Resistance againstLeishmania braziliensisInfection

Novais

Santiago²,

Báfica³

et al. 2009

The Journal of Immunology

132

121

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Neutrophils play an active role in the control of infections caused by intracellular pathogens such as Leishmania. In the present study, we investigated the effect of neutrophil depletion at the time of Leishmania braziliensis infection of BALB/c mice and how neutrophils interact with the infected macrophage to promote parasite elimination. The in vivo depletion of neutrophils led to a significant increase in parasite load and enhanced the Th1-Th2 immune response in this experimental model of infection. BALB/c mice coinoculated with both parasites and live neutrophils displayed lower parasite burdens at the site of infection and in the draining lymph nodes. In vitro, we observed that live neutrophils significantly reduced the parasite load in L. braziliensis-infected murine macrophages, an effect not observed with Leishmania major. L. braziliensis elimination was dependent on the interaction between neutrophils and macrophages and was associated with TNF-α as well as superoxide production. Furthermore, cooperation between neutrophils and macrophages toward parasite elimination was also observed in experiments performed with L. braziliensis-infected human cells and, importantly, with two other New World Leishmania species. These results indicate that neutrophils play an important and previously unappreciated role in L. braziliensis infection, favoring the induction of a protective immune response.

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Cooperative Role of Macrophages and Neutrophils in Host Antiprotozoan Resistance in Mice Acutely Infected withCryptosporidium parvum

Abstract: Severe experimental infections with

Cited by 37 publications

References 49 publications

Roles for NK Cells and an NK Cell-Independent Source of Intestinal Gamma Interferon for Innate Immunity toCryptosporidium parvumInfection

Roles for NK Cells and an NK Cell-Independent Source of Intestinal Gamma Interferon for Innate Immunity toCryptosporidium parvumInfection

Human Leukocytes Kill Brugia malayi Microfilariae Independently of DNA-Based Extracellular Trap Release

Neutrophils and Macrophages Cooperate in Host Resistance againstLeishmania braziliensisInfection

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