CD22 Is Required for Protection against West Nile Virus Infection

Abstract

West Nile virus (WNV) is a RNA virus of the family Flaviviridae and the leading cause of mosquito-borne encephalitis in the United States. Humoral immunity is essential for protection against WNV infection; however, the requirements for initiating effective antibody responses against WNV infection are still unclear. CD22 (Siglec-2) is expressed on B cells and regulates B cell receptor signaling, cell survival, proliferation, and antibody production. In this study, we investigated how CD22 contributes to protection against WNV infection and found that CD22 knockout (Cd22 ؊/؊ ) mice were highly susceptible to WNV infection and had increased viral loads in the serum and central nervous system (CNS) compared to wildtype (WT) mice. This was not due to a defect in humoral immunity, as Cd22 ؊/؊ mice had normal WNV-specific antibody responses. However, Cd22 ؊/؊ mice had decreased WNV-specific CD8 ؉ T cell responses compared to those of WT mice. These defects were not simply due to reduced cytotoxic activity or increased cell death but, rather, were associated with decreased lymphocyte migration into the draining lymph nodes (dLNs) of infected Cd22 ؊/؊ mice. Cd22 ؊/؊ mice had reduced production of the chemokine CCL3 in the dLNs after infection, suggesting that CD22 affects chemotaxis via controlling chemokine production. CD22 was not restricted to B cells but was also expressed on a subset of splenic DCIR2؉ dendritic cells that rapidly expand early after WNV infection. Thus, CD22 plays an essential role in controlling WNV infection by governing cell migration and CD8 ؉ T cell responses.

The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection

“…Conversely, CD22 has been shown to play a role in controlling a viral infection. CD22-deficient mice are more susceptible to West Nile Virus (WNV) infection, after which there was normal anti-WNV antibody production but decreased WNV-specific CD8 + T cell responses compared to wild type mice, including decreased lymphocyte migration into the draining lymph nodes [22].…”

Protection of mice deficient in mature B cells from West Nile virus infection by passive and active immunization

“…WNV-specific IgM and total IgG levels were determined by an ELISA using a purified recombinant WNV E protein as described [ 20 ]. In some experiments the quantities of serum WNV E-specific IgM and IgG between WT mice and BAFFR -/- mice were determined using the endpoint titer determination method [ 67 ]. In other experiments, to determine the specific amount of WNV E-specific IgM and IgG an adaptation of a previously described ELISA was used [ 27 ].…”

Sialic Acids in the Immune Response during Sepsis

“…That provided a potential therapeutic target to restore the immune homeostasis in sepsis ( 27 ). What is more, a recent Siglec-2 −/− mice study confirmed that Siglec-2 helped to control West Nile virus infection through CD8 T cells response, promoted lymphocyte migration into the draining lymph nodes, and affected chemotaxis via controlling chemokine production ( 28 ). Siglec-2 specific immunotoxins have been used in clinical studies for hairy cell leukemia and autoimmune diseases ( 29 , 30 ), however, studies on the sepsis is still lacking.…”