Effectors of innate immunity determination

A method of identifying a pattern of polynucleotide expression for inhibition of an inflammatory or septic response comprising:

• contacting cells with LPS, LTA, CpG DNA and/or intact bacteria or bacterial components in the presence or absence of a cationic peptide;
• detecting a pattern of polynucleotide expression for the cells in the presence and absence of the peptide, wherein the pattern in the presence of the peptide represents inhibition of an inflammatory or septic response.

A method of identifying an agent that enhances innate immunity comprising:

• contacting a polynucleotide or polynucleotides that encode a polypeptide involved in innate immunity, with an agent of interest, wherein expression of the polynucleotide in the presence of the agent is modulated as compared with expression of the polynucleotide in the absence of the agent and wherein the modulated expression results in enhancement of innate immunity.

The method of claim 23, wherein the interleukin is IL-8.

A method of identifying a pattern of polynucleotide expression for identification of a compound that selectively enhances innate immunity comprising:

• detecting a pattern of polynucleotide expression for cells contacted in the presence and absence of a cationic peptide, wherein the pattern in the presence of the peptide represents stimulation of innate immunity;
• detecting a pattern of polynucleotide expression for cells contacted in the presence of a test compound, wherein a pattern with the test compound that is similar to the pattern observed in the presence of the cationic peptide, is indicative of a compound that enhances innate immunity.

A method of identifying an agent that is capable of selectively enhancing innate immunity comprising:

• contacting a cell containing a polynucleotide or polynucleotides that encode a polypeptide involved in innate immunity, with an agent of interest, wherein expression of the polynucleotide or polynucleotides in the presence of the agent is modulated as compared with expression in the absence of the agent and wherein the modulated expression results in enhancement of innate immunity.

A method of identifying an agent that is capable of both suppressing or blocking septic or inflammatory responses and enhancing innate immunity comprising:

• contacting a cell containing i) a polynucleotide or polynucleotides that encode a polypeptide capable of suppressing inflammatory or septic responses and ii) a polynucleotide or polynucleotides that encode a polypeptide involved in innate immunity, with an agent of interest, wherein expression of in the presence of the agent is modulated as compared with expression of the polynucleotide or polynucleotides in the absence of the agent and wherein the modulated expression results in suppression of inflammatory or septic responses and enhancement of innate immunity.

A method for inferring a state of infection in a mammalian subject from a nucleic acid sample of the subject comprising identifying in the nucleic acid sample a polynucleotide expression pattern exemplified by an increase in polynucleotide expression of at least 2 polynucleotides in Table 55 as compared to a non-infected subject.

A method for inferring a state of infection in a mammalian subject from a nucleic acid sample of the subject comprising identifying in the nucleic acid sample a polynucleotide expression pattern exemplified by a decrease in polynucleotide expression of at least 2 polynucleotides in Table 56 as compared to a non-infected subject.

A method for inferring a state of infection in a mammalian subject from a nucleic acid sample of the subject comprising identifying in the nucleic acid sample a polynucleotide expression pattern exemplified by a polynucleotide expression of at least 2 polynucleotides in Table 57 as compared to a non-infected subject.

A cationic peptide that is an antagonist of CXCR-4.

A method of identifying a cationic peptide that is an antagonist of CXCR-4 comprising contacting T cells with SDF-1 in the presence of absence of a test peptide and measuring chemotaxis, wherein a decrease in chemotaxis in the presence of the test peptide is indicative of a peptide that is an antagonist of CXCR-4.

An isolated cationic peptide comprising the general formula X1X2X3IX4PX4IPX5X2X1 (SEQ ID NO:

• 4), wherein X1 is one or two of R, L or K, X2 is one of C, S or A, X3 is one of R or P, X4 is one of A or V and X5 is one of V or W.

An isolated cationic peptide comprising the general formula X1LX2X3KX4X2X5X3PX3X1 (SEQ ID NO:

• 11), wherein X1 is one or two of D, E, S, T or N, X2 is one or two of P, G or D, X3 is one of G, A, V, L, I or Y, X4 is one of R, K or H and X5 is one of S, T, C, M or R.

An isolated cationic peptide comprising the general formula X1X2X3X4WX4WX4X5K (SEQ ID NO:

• 18), wherein X1 is one to four chosen from A, P or R, X2 is one or two aromatic amino acids (F, Y and W), X3 is one of P or K, X4 is one, two or none chosen from A, P, Y or W and X5 is one to three chosen from R or P.

An isolated cationic peptide comprising the general formula X1X2X3X4X1VX3X4RGX4X3X4X1X3X1 (SEQ ID NO:

• 25) wherein X1 is one or two of R or K, X2 is a polar or charged amino acid (S, T, M, N, Q, D, E, K, R and H), X3 is C, S, M, D or A and X4 is F, I, V, M or R.

An isolated cationic peptide comprising the general formula X1X2X3X4X1VX5X4RGX4X5X4X1X3X1 (SEQ ID NO:

• 32), wherein X1 is one or two of R or K, X2 is a polar or charged amino acid (S, T, M, N, Q, D, E, K, R and H), X3 is one of C, S, M, D or A, X4 is one of F, I, V, M or Rand X5 is one of A, I, S, M, D or R.

An isolated cationic peptide comprising the general formula KX1KX2FX2KMLMX2ALKKX3 (SEQ ID NO:

• 39), wherein X1 is a polar amino acid (C, S, T, M, N and Q);
• X2 is one of A, L, S or K and X3 is 1-17 amino acids chosen from G, A, V, L, I, P, F, S, T, K and H.

An isolated cationic peptide comprising the general formula KWKX2X1X1X2X2XX2X2X1X1X2X2IFHTALKPISS (SEQ ID NO:

• 46), wherein X1 is a hydrophobic amino acid and X2 is a hydrophilic amino acid.

An isolated cationic peptide comprising the sequence KWKSFLRTFKSPVRTVFHTALKPISS (SEQ ID NO:

• 53).

An isolated cationic peptide comprising the sequence KWKSYAHTIMSPVRLVFHTALKPISS (SEQ ID NO:

• 54).

An isolated cationic peptide that reduces polynucleotide expression of SDF-1 receptor.