Role of lipopolysaccharide in induction of Ia expression during infection with gram-negative bacteria

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Lipopolysaccharide (LPS), a major component of the outer membrane of gram-negative bacteria, is known to be a potent modulator of many host immune functions, including the expression of products of the class II major histocompatibility locus (Ia molecules) by macrophages. LPS-mediated Ia induction is controlled by the lps gene. We sought to determine the role of LPS in the induction of Ia expression during infection with gram-negative bacteria. To address this question, we tested a simple prediction: if LPS is the primary determinant of Ia induction during gram-negative infection, then the Ia response to intraperitoneal injection of these organisms should be under the control of the lps gene. We found that while both LPS-responder and LPS-low-responder mice showed strong Ia responses to injection of either a gram-positive bacterium (Listeria monocytogenes) or concanavalin A, only the LPS-responder mice responded strongly to gram-negative organisms or to LPS alone. We interpret these results as strong evidence for the role of LPS as the primary determinant of Ia induction by gram-negative bacteria.