Stronger In Vitro Phagocytosis by Monocytes-Macrophages Is Indicative of Greater Pathogen Clearance and Antibody Levels In Vivo

Sun, Shanfeng; Qiu-zhen, Pan; Hui, Xin; Zhang, B. L.; Wu, Hongping; Li, Hao; Xu, Wenbo; Zhang, Q.; Li, J. Y.; Deng, Xuemei; Chen, J. W.; Lian, Zhengxing; Li, N.

doi:10.3382/ps.2007-00202

Cited by 31 publications

(23 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These cells, however, neither express FcγR naturally nor are primary targets of dengue virus in human infections. Monocytes, on the other hand, play a central role in DENV replication (30) as well as in the removal of the antibody-virus complex in vivo (31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection

Chan

Zhang²,

Tan

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

128

136

View full text Add to dashboard Cite

The interaction of antibodies, dengue virus (DENV), and monocytes can result in either immunity or enhanced virus infection. These opposing outcomes of dengue antibodies have hampered dengue vaccine development. Recent studies have shown that antibodies neutralize DENV by either preventing virus attachment to cellular receptors or inhibiting viral fusion intracellularly. However, whether the antibody blocks attachment or fusion, the resulting immune complexes are expected to be phagocytosed by Fc gamma receptor (FcγR)-bearing cells and cleared from circulation. This suggests that only antibodies that are able to block fusion intracellularly would be able to neutralize DENV upon FcγR-mediated uptake by monocytes whereas other antibodies would have resulted in enhancement of DENV replication. Using convalescent sera from dengue patients, we observed that neutralization of the homologous serotypes occurred despite FcγR-mediated uptake. However, FcγR-mediated uptake appeared to be inhibited when neutralized heterologous DENV serotypes were used instead. We demonstrate that this inhibition occurred through the formation of viral aggregates by antibodies in a concentration-dependent manner. Aggregation of viruses enabled antibodies to cross-link the inhibitory FcγRIIB, which is expressed at low levels but which inhibits FcγR-mediated phagocytosis and hence prevents antibody-dependent enhancement of DENV infection in monocytes. D engue is the most common mosquito-borne viral disease globally. The lack of an effective preventive measure, especially a licensed vaccine, has resulted in the global spread of this virus (1, 2). Although neutralizing antibodies can confer lifelong immunity against reinfection by one of the four dengue virus (DENV) serotypes, subneutralizing antibody levels or crossreactive antibodies appear to enhance the risk of severe dengue in subsequent infections (3-6). DENV bound with subneutralizing concentrations of antibody has been shown to result in increased virus uptake and replication in Fc gamma receptor (FcγR)-bearing cells such as monocytes/macrophages (4, 7). Thus, defining the determinants for virus neutralization will be important for the design of an effective dengue vaccine that protects against all four DENV serotypes while minimizing the risk of antibodydependent enhancement of DENV infection.Neutralization of flavivirus infection is a multiple-hit phenomenon. Recent stoichiometric studies have shown that both antibody affinity and epitope accessibility are important determinants for virus neutralization (8-10). Antibodies neutralize DENV by either preventing virus attachment to cellular receptors (11) or inhibiting viral fusion intracellularly (12). However, whether the antibody blocks attachment or fusion, the resulting immune complex is expected to be cleared from the circulation by professional phagocytes, especially the FcγR-bearing cells. This suggests that only antibodies that are able to block fusion intracellularly would be able to neutralize DENV upon FcγR-mediated uptake by ...

show abstract

Section: Discussionmentioning

confidence: 99%

Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection

Chan

Zhang²,

Tan

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

128

136

View full text Add to dashboard Cite

show abstract

“…Monocytes, which are isolated from PBMC by exploiting their ability to adhere to glass or plastic, constitute a major phagocytic cellular component in the blood. With culture in vitro, monocytes became monocytes-macrophages lineage positive for CD14 (Sun et al, 2008). Monocytes-macrophages are important regulators in both innate and adaptive immunity.…”

Section: Discussionmentioning

confidence: 99%

“…After 24 h of incubation, PBMC were washed 3 times with PBS and the nonadherent cells (most of the lymphocytes and thrombocytes) were washed out. After 48 h of incubation and washing away nonadherent cells, approximately 90% of the adherent cells were monocytes-macrophages Sun et al, 2008).…”

Section: Cell Isolation and Culturementioning

confidence: 99%

“…Phagocytosis was allowed to occur over the ensuing 6 h at 37°C in a 5% CO 2 incubator. The counting method was as described in Sun et al (2008). Briefly, after incubation, the cells were washed twice with PBS.…”

Section: Phagocytosis Assaymentioning

confidence: 99%

“…The recorded titer of 1:1 was the undiluted serum, and the antibody titer of the sample was the highest dilution at minimal positive response. The positive and negative sera (China Institute of Veterinary Drug Control) were used as positive and negative controls (Sun et al, 2008).…”

Section: Slide Agglutination For Antibody Titermentioning

confidence: 99%

See 2 more Smart Citations

Monocytes-macrophages phagocytosis as a potential marker for disease resistance in generation 1 of dwarf chickens

Ning

Yi-chen

et al. 2010

Poultry Science

Self Cite

View full text Add to dashboard Cite

Monocytes-macrophages play an indispensable role in the immune system. The current study investigated the effect of selection for monocytes-macrophages phagocytosis on disease resistance in generation 1 (G1) of dwarf chickens. Five hundred dwarf chickens of generation 0 (G0) were divided into high and low phagocytic index (PI) groups (HPIG and LPIG, respectively) based on their PI of monocytes-macrophages at 290 d of age. Then, 2 x 2 mating combinations were conducted. Sixty G0 chickens from another dwarf chicken group were used to measure the levels of monocytes-macrophages phagocytosis at different developmental stages. Among a total of 2,500 randomly selected G1 chickens, 2,100 individuals were used for a surviving and growing test under adverse feeding circumstances, and the other 400 individuals were tested for Salmonella Pullorum challenge. The results showed that progenies of HPIG hens (female symbol) were more resistant to Salmonella Pullorum. After challenge, the death rate of progeny from HPIG female symbol (28.9%) was only 58% that of progeny from LPIG female symbol (49.4%, P < 0.001). In addition, the natural infection rate of Salmonella Pullorum before 207 d for offspring from HPIG female symbol (35.0%) was significantly lower than that for offspring from LPIG female symbol (48.3%, P < 0.001). The natural mortality before 56 d in progeny of HPIG female symbol (22.6%) was significantly lower than that in progeny of LPIG female symbol (29.1%) with a P-value of 0.001. The G1 chickens of HPIG G0 female symbol weighed more than those born to LPIG G0 female symbol at 28 and 42 d of age, whereas the difference was not statistically significant at 56 d of age. The heritability of monocytes-macrophages phagocytosis was 0.40, which was moderate. The PI values were at a low level before 126 d and increased dramatically until they declined significantly after 294 d. It could be concluded that phagocytosis of monocytes-macrophages is a marker for breeding excellent progeny with strong disease resistance.

show abstract

The protein-tyrosine phosphatase DEP-1 promotes migration and phagocytic activity of microglial cells in part through negative regulation of fyn tyrosine kinase

Schneble

Müller

Kliche

et al. 2016

Glia

View full text Add to dashboard Cite

Microglia cells are brain macrophages whose proper functioning is essential for maintenance and repair processes of the central nervous system (CNS). Migration and phagocytosis are critical aspects of microglial activity. By using genetically modified cell lines and knockout mice we demonstrate here that the receptor protein-tyrosine phosphatase (PTP) DEP-1 (also known as PTPRJ or CD148) acts as a positive regulator of both processes in vitro and in vivo. Notably, reduced microglial migration was detectable in brains of Ptprj mice using a wounding assay. Mechanistically, density-enhanced phosphatase-1 (DEP-1) may in part function by inhibiting the activity of the Src family kinase Fyn. In the microglial cell line BV2 DEP-1 depletion by shRNA-mediated knockdown resulted in enhanced phosphorylation of the Fyn activating tyrosine (Tyr ) and elevated specific Fyn-kinase activity in immunoprecipitates. Moreover, Fyn mRNA and protein levels were reduced in DEP-1 deficient microglia cells. Consistent with a negative regulatory role of Fyn for microglial functions, which is inhibited by DEP-1, microglial cells from Fyn mice exhibited elevated migration and phagocytosis. Enhanced microglia migration to a site of injury was also observed in Fyn mice in vivo. Taken together our data revealed a previously unrecognized role of DEP-1 and suggest the existence of a potential DEP-1-Fyn axis in the regulation of microglial functions. GLIA 2017;65:416-428.

show abstract

Stronger In Vitro Phagocytosis by Monocytes-Macrophages Is Indicative of Greater Pathogen Clearance and Antibody Levels In Vivo

Cited by 31 publications

References 31 publications

Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection

Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection

Monocytes-macrophages phagocytosis as a potential marker for disease resistance in generation 1 of dwarf chickens

The protein-tyrosine phosphatase DEP-1 promotes migration and phagocytic activity of microglial cells in part through negative regulation of fyn tyrosine kinase

Contact Info

Product

Resources

About